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Found 440 gene(s). Export as Excel file, text file

Victors ID Gene Name Sequence Strain (Species/Organism) NCBI Gene ID NCBI Nucleotide GI NCBI Protein GI Locus Tag Genbank Accession Protein Accession Protein Name Molecule Role Molecule Role Annotation PMID
957 rbsK from Brucella suis 1330 Brucella suis 1330 1164441 23499772 BRA0005 NP_699212.1 ribokinase, putative Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: Ribokinase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
958 mgtB from Brucella suis 1330 Brucella suis 1330 1164473 23499804 BRA0037 NP_699244.1 magnesium ion-transporting ATPase, E1-E2 family Virulence factor FUNCTIONAL GROUP: Metal acquisition (Delrue et al., 2004).

FUNCTION: Mg2+ uptake (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
959 nodV from Brucella suis 1330 Brucella suis 1330 1164477 23499808 BRA0041 NP_699248.1 sensor histidine kinase Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Histidine kinase (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
960 gltD from Brucella suis 1330 Brucella suis 1330 1164492 23499822 BRA0055 NP_699262.1 glutamate synthase subunit beta Virulence factor MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus (Hong et al., 2000). 10858227
961 virB11 from Brucella suis 1330 Brucella suis 1330 1164496 23499826 BRA0059 AE014292 NP_699266 type IV secretion system protein VirB11 Virulence factor MUTATION: The virB11 mutation experiment confirms that a complete VirB apparatus is required for their secretion (Marchesini et al., 2004). 15312849
962 virB10 Brucella suis 1330 1164497 23499827 BRA0060 AE014292 NP_699267 type IV secretion system protein VirB10 Virulence factor MUTATION: Mutants with polar and nonpolar mutations introduced in irB10 showed different behaviors in mice and in the HeLa cell infection assay, suggesting that virB10 per se is necessary for the correct function of this type IV secretion apparatus (Comerci et al., 2001).

A B. abortus virB10 mutant showed a decrease of intracellular live bacteria comparable to that of the wild-type strain until 4 h after infection, indicating that a functional VirB system is not required for the short-term survival of Brucella inside macrophages. At later time points, the number of live virB10 mutants progressively decreased. Hence, the Brucella virB10 strain did not replicate, but rather was killed. Although the virB10 mutants are capable of short-term survival, they can not evade long-term degradation through fusion with lysosomes (Comerci et al., 2001).

B abortus virB1 and virB10 mutants are unable to persist in mouse spleens after i.p. inoculation, suggest that attenuation in the animal model is due to an inability of these strains to grow intracellularly (Comerci et al., 2001).

A B abortus virB10 mutant lost the ability to multiply in HeLa cells and was not recovered from the spleens of infected BALBc mice (Comerci et al., 2001).

The non polar virB10 mutant was able to block the acquisition of cathepsin D, but was not able to translocate to the replication compartment (Comerci et al., 2001).

The virB10 non-polar mutants were capable of avoiding interactions with the endocytic pathway but , diverging to wild-type Brucella, were unable to reach the endoplasmic reticulum to establish their intracellular replication niche and seemed to be recycled to the cell surface (Comerci et al., 2001).
11260139
963 virB9 from Brucella suis 1330 Brucella suis 1330 1164498 23499828 BRA0061 NP_699268.1 type IV secretion system protein VirB9 Virulence factor MUTATION: Uptake in the presence or absence of Ca2 and Mg2 did not influence the subsequent intracellular survival of wild-type Brucella, whereas the decrease in the number of surviving virB9 mutant cells was delayed in the absence of Ca2 and Mg2. Possibly two types of adhesion molecules promoted uptake of Brucella, one being Ca2 and Mg2 dependent and the other not, and that both types participate in the uptake of wild-type bacteria but only the latter type participates in the uptake of the virB9 mutant (Gorvel and Moreno, 2002).

Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages (Gorvel and Moreno, 2002).

The intracellular fate of three virB mutants (virB2, virB4 and virB9) in HeLa cells by immunofluorescence was examined. The three VirB proteins are not necessary for penetration and the inhibition of phago-lysosomal fusion within non-professional phagocytes. Rather, the virB mutants are unable to reach the replicative niche and reside in a membrane -bound vacuole expressing the late endosomal marker, LAMP1, and the sec61beta protein from the ER membrane, proteins that are present in autophagic vesicles originating from the ER (Gorvel and Moreno, 2002).

Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1 -positive early compartments and then localize in LAMP1-positive compartments at early times of infection (Gorvel and Moreno, 2002).
12414149
964 virB8 from Brucella suis 1330 Brucella suis 1330 1164499 23499829 BRA0062 NP_699269.1 type IV secretion system protein VirB8 Virulence factor MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis (Gorvel and Moreno, 2002). Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection (Gorvel and Moreno, 2002). 12414149
965 virB6 from Brucella suis 1330 Brucella suis 1330 1164501 23499831 BRA0064 NP_699271.1 type IV secretion system protein VirB6 Virulence factor MUTATION: B. abortus virB6 is essential for intracellular growth within HeLa cells as shown from a mutagenesis study.
966 virB5 from Brucella suis 1330 Brucella suis 1330 1164502 23499832 BRA0065 NP_699272.1 type IV secretion system protein VirB5 Virulence factor MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon (O'Callaghan et al., 1999).

Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion (O'Callaghan et al., 1999).

Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels (O'Callaghan et al., 1999).

Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages (O'Callaghan et al., 1999).
10510235
967 virB4 from Brucella suis 1330 Brucella suis 1330 1164503 23499833 BRA0066 NP_699273.1 type IV secretion system protein VirB4 Virulence factor MUTATION: A mutant strain of B abortus that contains an in-frame deletion in virB4 is unable to replicate in macrophages and survives in mice (Kim et al., 2004). ntracellular replication was inhibited in wild-type B abortus after introducing a plasmid expressing a mutant VirB4 altered in the NTP -binding region. VirB4 containing the intact NTP -binding region is essential for evasion of fusion with lysosomes (11988518).

The ruffling associated with internalization of the virB4 mutant results in a more rapid uptake than for the wild-type strain. The virB4 mutant shows primarily small regions of phalloidin staining at the sites of binding. Macrophages incubated simultaneously with B abortus and the fluid-phase marker tetramethyl rhodamine isothiocyanate (TRITC)-dextran accumulate the marker in large vacuoles containing the wild-type strain, but little or no marker accumulates in phagosomes containing the virB4 mutant. Similarly, phase-contrast micrographs have shown the wild-type strain in large phase-transparent compartments, but the virB4 mutant is in much smaller compartments (14738898).

Intracellular growth-defective virB4 mutant and attenuated vaccine strain S19 did not induce abortion (Kim et al., 2004).

The B abortus virB4 mutant was completely cleared from the spleens of mice after 4 weeks, while the pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from spleens after 10 weeks. Splenomegaly was not observed at all in mice infected with virB4 mutant (Kim et al., 2004).
15135535
968 virB3 from Brucella suis 1330 Brucella suis 1330 1164504 23499834 BRA0067 NP_699274.1 type IV secretion system protein VirB3 Virulence factor MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells (Kim et al., 2003). 12761078
969 virB2 from Brucella suis 1330 Brucella suis 1330 1164505 23499835 BRA0068 NP_699275.1 type IV secretion system protein VirB2 Virulence factor MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection (Sun et al., 2005).

Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis (Sun et al., 2005).
16113325
970 virB1 Brucella suis 1330 1164506 23499836 BRA0069 AE014292 NP_699276 type IV secretion system protein VirB1 Virulence factor MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB1 mutant persisted at wild-type levels, showing that the function of VirB1 is dispensable in the mouse model of persistent infection (Höppner et al., 2005).

A B abortus polar virB1 mutant failed to replicate in HeLa cells, indicating that the virB operon plays a critical role in intracellular multiplication (Höppner et al., 2005).

Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis (Höppner et al., 2005).

An infection assay with signature-tagged Brucella abortus mutants demonstrated that mutagenesis of the virB1 gene causes attenuation of virulence (Höppner et al., 2005).
16272371
971 hemH from Brucella suis 1330 Brucella suis 1330 1164513 23499843 BRA0076 NP_699283.1 ferrochelatase Virulence factor FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(UniProt: P0A3D7).

CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(UniProt: P0A3D7).

PATHWAY: Protoheme biosynthesis; last step(UniProt: P0A3D7).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: P0A3D7).

SIMILARITY: Belongs to the ferrochelatase family(UniProt: P0A3D7).

MUTATION: A hemH knockout B. abortus mutant displayed auxotrophy for hemin, defective intracellular survival inside J774 and HeLa cells, and lack of virulence in BALBc mice. This phenotype was overcome by complementing the mutant strain with a plasmid harboring wild-type hemH. These data demonstrate that B abortus synthesizes its own heme and also has the ability to use an external source of heme (Almirón et al., 2001).
11553564
972 omp10 from Brucella suis 1330 Brucella suis 1330 1164514 23499844 BRA0077 NP_699284.1 lipoprotein Omp10 Virulence factor SUBCELLULAR LOCATION: Outer membrane; lipid-anchor(UniProt: P0A3N9).

MISCELLANEOUS: Elicits an immune response in B.melitensis-infected sheep but not in B.abortus-infected cattle(UniProt: P0A3N9).

SIMILARITY: Belongs to the rhizobiaceae omp10 lipoprotein family(UniProt: P0A3N9).

MUTATION: Omp10 is an immunoreactive outer membrane lipoprotein. The omp10 mutant was dramatically attenuated for survival in mice and was defective for growth in minimal medium but was not impaired in intracellular growth in vitro, nor does it display clear modification of the outer membrane properties (Tibor et al., 2002).
12228280
973 gnd from Brucella suis 1330 Brucella suis 1330 1164548 23499876 BRA0111 NP_699316.1 6-phosphogluconate dehydrogenase Virulence factor MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model (Kim et al., 2003). 12761078
974 vjbR from Brucella suis 1330 Brucella suis 1330 1164556 23499883 BRA0119 NP_699323.1 transcriptional regulator, LuxR family Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Transcriptional regulator (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
975 gtrB from Brucella suis 1330 Brucella suis 1330 1164572 23499898 BRA0135 NP_699338.1 glycosyl transferase, group 2 family protein Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: glycosyl transerase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
976 deoR from Brucella suis 1330 Brucella suis 1330 1164583 23499909 BRA0146 NP_699349.1 transcriptional regulator, DeoR family Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Transcriptional regulator (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
977 flgI from Brucella suis 1330 Brucella suis 1330 1164593 161486704 BRA0156 NP_699358.2 flagellar basal body P-ring protein Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (Delrue et al., 2004).

FUNCTION: P-ring (Delrue et al., 2004).

MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (Delrue et al., 2004).
14979322
978 gntR from Brucella suis 1330 Brucella suis 1330 1164614 23499939 BRA0177 NP_699379.1 transcriptional regulator, GntR family Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Transcriptional regulator (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
979 gluP from Brucella suis 1330 Brucella suis 1330 1164627 0 BRA0190 - - Virulence factor FUNCTION: Intake of glucose and galactose (Potential)(UniProt: Q8YB48).

SUBCELLULAR LOCATION: Inner membrane; multi-pass membrane protein (Probable)(UniProt: Q8YB48).

SIMILARITY: Belongs to the major facilitator superfamily. FHS transporter (TC 2.A.1.7) family(UniProt: Q8YB48).

MUTATION: B suis and maybe B canis seem to have two glucosegalactose transporters: gluP and gguAB. B abortus may express only gluP, which may explain why gluP mutants fail to survive long periods in the mouse (Essenberg et al., 2002).
12414147
980 caiB from Brucella suis 1330 Brucella suis 1330 1164661 23499983 BRA0224 NP_699423.1 CAIB/BAIF family protein Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: CAIB/BAIF family (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
981 norE from Brucella suis 1330 Brucella suis 1330 1164683 23500003 BRA0246 NP_699443.1 cytochrome c oxidase, subunit III Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Nitric oxide reduction (Delrue et al., 2004).

MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (Delrue et al., 2004).
14979322
982 norD Brucella 1164688 23500008 BRA0251 NP_699448.1 norD protein Virulence factor MUTATION: A mutant of Brucella suis bearing a Tn5 insertion in norD , the last gene of the operon norEFCBQD, encoding nitric oxide reductase, was unable to survive under anaerobic denitrifying conditions (more-than-5log reduction in viable counts). As a consequence of the norD mutation , NO might not be further reduced to N2O by the NO reductase and it could become toxic for the bacteria. The infection of resting macrophages showed that the norD mutant and the wild-type strain displayed similar rates of multiplication. On the contrary, activation of J774A.1 cells by LPS and IFN was accompanied by a more-thantenfold attenuation of the norD mutant at 48 h p. i. (Loisel-Meyer et al., 2006). 16495577
983 narG from Brucella suis 1330 Brucella suis 1330 1164736 23500054 BRA0299 NP_699494.1 respiratory nitrate reductase, alpha subunit Virulence factor MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate (Kohler et al., 2002). A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis xx gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). 12438693
984 nrdH from Brucella suis 1330 Brucella suis 1330 1164751 23500069 BRA0314 NP_699509.1 glutaredoxin-like protein nrdH Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Ribonucleotide recuctase (Delrue et al., 2004).

MUTATION: Attenuated in HeLa, but not in Macrophages, mice (Delrue et al., 2004).
14979322
985 wbpW from Brucella suis 1330 Brucella suis 1330 1164785 23500100 BRA0347 NP_699540.1 mannose-1-phosphate guanylyltransferase/mannose-6-phosphate isomerase Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
986 manB from Brucella suis 1330 Brucella suis 1330 1164786 23500101 BRA0348 NP_699541.1 phosphoglucomutase, putative Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
987 oxyR Brucella suis 1330 1164792 23500107 BRA0354 AE014292 NP_699547 transcriptional regulator OxyR Virulence factor MUTATION: The transcription product of Brucella abortus oxyR binds to the B abortus catalase promoter region. A gene replacementdeletion Brucella oxyR mutant exhibits increased sensitivity to prolonged exposure to H2O2 and is unable to adapt to H2O2 in the environment (Kim and Mayfield, 2000). 10986275
988 xfp from Brucella suis 1330 Brucella suis 1330 1164823 23500138 BRA0385 NP_699578.1 putative phosphoketolase Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Degradation (Delrue et al., 2004).

FUNCTION: Lys. degradation (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
989 glpK from Brucella suis 1330 Brucella suis 1330 1164881 23500192 BRA0443 NP_699632.1 glycerol kinase Virulence factor FUNCTION: Key enzyme in the regulation of glycerol uptake and metabolism(UniProt: Q8FWK8).

CATALYTIC ACTIVITY: ATP + glycerol = ADP + sn-glycerol 3-phosphate(UniProt: Q8FWK8).

PATHWAY: Glycerol utilization; first (rate-limiting) step(UniProt: Q8FWK8).

SIMILARITY: Belongs to the FGGY kinase family(UniProt: Q8FWK8).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
990 ssuB from Brucella suis 1330 Brucella suis 1330 1164905 23500215 BRA0467 NP_699655.1 taurine ABC transporter, permease protein, putative Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (Delrue et al., 2004).

FUNCTION: Permease (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
14979322
991 cydD from Brucella suis 1330 Brucella suis 1330 1164946 23500255 BRA0508 NP_699695.1 ABC transporter, ATP-binding protein CydD Virulence factor MUTATION: The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment (Kim et al., 2003). 12761078
992 cydC from Brucella suis 1330 Brucella suis 1330 1164947 23500256 BRA0509 NP_699696.1 ABC transporter, ATP-binding/permease protein Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Cytochrome oxidase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
993 cydB from Brucella suis 1330 Brucella suis 1330 1164949 23500258 BRA0511 NP_699698.1 cytochrome d ubiquinol oxidase, subunit II Virulence factor MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice (Endley et al., 2001). The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment (Endley et al., 2001). 11274104
994 rbsC from Brucella suis 1330 Brucella suis 1330 1165007 23500312 BRA0568 NP_699752.1 ABC transporter, permease protein Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (Delrue et al., 2004).

FUNCTION: ABC transporter (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
995 pcs Brucella suis 1330 1165011 23500316 BRA0572 AE014292 NP_699756 phosphatidylcholine synthase Virulence factor MUTATION: The role of Phosphatidylcholine (PC) in Brucella abortus was examined by generating mutants in pcs (BApcs) and pmtA (BApmtA), which encode key enzymes of the two bacterial PC biosynthetic routes, the choline and methyl-transferase pathways. In rich medium, BApcs and the double mutant BApcspmtA but not BApmtA displayed reduced growth, increased phosphatidylethanolamine and no PC, showing that Pcs is essential for PC synthesis under these conditions. In minimal medium, the parental strain, BApcs and BApmtA showed reduced but significant amounts of PC suggesting that PmtA may also be functional Probing with phage Tb, antibiotics, polycations and serum demonstrated that all mutants had altered envelopes. In macrophages, BApcs and BApcspmtA showed reduced ability to evade fusion with lysosomes and establish a replication niche. In mice, BApcs showed attenuation only at early times after infection, BApmtA at later stages and BApcspmtA throughout. The results suggest that Pcs and PmtA have complementary roles in vivo related to nutrient availability and that PC and the membrane properties that depend on this typical eukaryotic phospholipid are essential for Brucella virulence (Conde-Alvarez et al., 2006). 16882035
996 aidB from Brucella suis 1330 Brucella suis 1330 1165038 23500342 BRA0598 NP_699782.1 acyl-CoA dehydrogenase family protein Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Repair (Delrue et al., 2004).

FUNCTION: Protection against alkylation damage to DNA (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
997 pyrB from Brucella suis 1330 Brucella suis 1330 1165039 23500343 BRA0599 NP_699783.1 aspartate carbamoyltransferase catalytic subunit Virulence factor CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(UniProt: P65612).

PATHWAY: Nucleotide biosynthesis; UMP biosynthesis; UMP from HCO(3)(-): step 2(UniProt: P65612).

PATHWAY: Context: Pyrimidine biosynthesis(UniProt: P65612).

SIMILARITY: Belongs to the ATCase/OTCase family(UniProt: P65612).

MUTATION: B. abortus pyrB (pyrimidines) gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study (Kim et al., 2003).
12761078
998 divK from Brucella suis 1330 Brucella suis 1330 1165052 23500356 BRA0612 NP_699796.1 polar differentiation response regulator Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Response regulator (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
999 ugpB from Brucella suis 1330 Brucella suis 1330 1165097 23500399 BRA0655 NP_699839.1 glycerol-3-phosphate ABC transporter, periplasmic glycerol-3-phosphate-binding protein Virulence factor MUTATION: B suis ugpB mutant does not contain SP41 protein. Mutants lacking SP41 production are less invasive, but proliferate in HeLa cells. An isogenic DeltaugpB mutant showed a significant inhibitory effect on Brucella adherence and invasion of human cultured epithelial cells and this effect could be reversed by restoration of the ugpB on a plasmid. (Castañeda-Roldán et al., 2006). 16817909
1000 ugpA from Brucella suis 1330 Brucella suis 1330 1165098 23500400 BRA0656 NP_699840.1 glycerol-3-phosphate ABC transporter, permease protein Virulence factor MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice (Lestrate et al., 2003). 14638795
1001 ugpA from Brucella suis 1330 Brucella suis 1330 1165134 23500433 BRA0692 NP_699873.1 sugar ABC transporter, permease protein, putative Virulence factor MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice (Lestrate et al., 2003). 14638795
1002 fbpA from Brucella suis 1330 Brucella suis 1330 1165142 23500440 BRA0700 NP_699880.1 iron compound ABC transporter, periplasmic iron compound-binding protein, putative Virulence factor FUNCTIONAL GROUP: Metal acquisition (Delrue et al., 2004).

FUNCTION: Fe3+ binding (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
14979322
1003 sodC from Brucella suis 1330 Brucella suis 1330 1165145 23500443 BRA0703 NP_699883.1 superoxide dismutase, Cu-Zn Virulence factor FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(UniProt: P66827).

CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(UniProt: P66827).

COFACTOR: Binds 1 copper ion per subunit (By similarity)(UniProt: P66827).

COFACTOR: Binds 1 zinc ion per subunit (By similarity)(UniProt: P66827).

SUBUNIT: Homodimer (By similarity)(UniProt: P66827).

SUBCELLULAR LOCATION: Periplasmic (By similarity)(UniProt: P66827).

SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(UniProt: P66827).

IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-γ, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development (He et al., 2002; He et al., 2002; He et al., 2002).

MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages (He et al., 2002).
11953393
1004 RpiR from Brucella suis 1330 Brucella suis 1330 1165154 23500452 BRA0712 NP_699892.1 SIS domain protein Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Transcriptional regulator (Delrue et al., 2004).

MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (Delrue et al., 2004).
14979322
1005 gcvP from Brucella suis 1330 Brucella suis 1330 1165167 23500462 BRA0725 NP_699902.1 glycine dehydrogenase Virulence factor FUNCTION: The glycine cleavage system catalyzes the degradation of glycine. The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (By similarity)(UniProt: Q8FVU9).

CATALYTIC ACTIVITY: Glycine + H-protein-lipoyllysine = H-protein-S-aminomethyldihydrolipoyllysine + CO(2)(UniProt: Q8FVU9).

COFACTOR: Pyridoxal phosphate (By similarity)(UniProt: Q8FVU9).

SUBUNIT: The glycine cleavage system is composed of four proteins: P, T, L and H (By similarity)(UniProt: Q8FVU9).

SIMILARITY: Belongs to the gcvP family(UniProt: Q8FVU9).

MUTATION: gcvP encodes for glycine dehydrogenase and is required for persistent infection in mouse model (Ficht, 2003).
12523983
1006 gcvT from Brucella suis 1330 Brucella suis 1330 1165169 23500464 BRA0727 NP_699904.1 glycine cleavage system T protein Virulence factor MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis gcvT gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). 12438693
1007 xseA from Brucella suis 1330 Brucella suis 1330 1165206 23500501 BRA0764 NP_699941.1 exodeoxyribonuclease VII large subunit Virulence factor FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(UniProt: Q8FVR1).

CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(UniProt: Q8FVR1).

SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(UniProt: Q8FVR1).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8FVR1).

SIMILARITY: Belongs to the xseA family(UniProt: Q8FVR1).

MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice (Lestrate et al., 2003).
14638795
1008 zwf from Brucella suis 1330 Brucella suis 1330 1165220 23500514 BRA0778 NP_699954.1 glucose-6-phosphate 1-dehydrogenase Virulence factor MUTATION: Brucella abortus zwf mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells and macrophages (Kim et al., 2003). 12761078
1009 nikA from Brucella suis 1330 Brucella suis 1330 1165246 23500537 BRA0804 NP_699977.1 nickel ABC transporter, nickel-binding protein, putative Virulence factor FUNCTIONAL GROUP: Metal acquisition (Delrue et al., 2004).

FUNCTION: Ni2+ uptake (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages, Mice (Delrue et al., 2004).
14979322
1010 galcD from Brucella suis 1330 Brucella suis 1330 1165248 23500539 BRA0806 NP_699979.1 hydrolase, UxaA family Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: D-galactarate dehydratase (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1011 eryB from Brucella suis 1330 Brucella suis 1330 1165308 23500593 BRA0865 NP_700033.1 glycerol-3-phosphate dehydrogenase Virulence factor MUTATION: EryB is an erythritol phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 (Sangari et al., 2000).

The B. suis eryB mutant by Tn5 transposon mutagenesis was attenuated in the human macrophage -like THP-1 cells. This mutant is sensitive to erythritol and mimics the erythritol sensitive response of the B19 strain (Sangari et al., 2000).
10708387
1012 eryC from Brucella suis 1330 Brucella suis 1330 1165309 23500594 BRA0866 NP_700034.1 D-erythrulose-1-phosphate dehydrogenase Virulence factor MUTATION: The eryC gene encodes for enzyme Derythrulose-1-phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 (Sangari et al., 2000).

Allelic exchange mutants in eryC of Brucella suis were erythritol sensitive in vitro with a MIC of 1 to 5 mM of erythritol. Their multiplication in macrophage-like cells was 50 to 90- fold reduced , but complementation of the mutant restored wild-type levels of intracellular multiplication and the capacity to use erythritol as a sole carbon source. In vivo, the eryC mutant colonized the spleens of infected BALBc mice to a significantly lower extent than the wild type and the complemented strain. Interestingly, eryC mutants that were in addition spontaneously erythritol tolerant nevertheless exhibited wild-type-like intramacrophagic and intramurine replication. In conclusion, erythritol was not an essential carbon source for the pathogen in the macrophage host cell but that the inactivation of the eryC gene significantly reduced the intramacrophagic and intramurine fitness of B suis (Sangari et al., 2000).
10708387
1013 fdhA from Brucella suis 1330 Brucella suis 1330 1165363 23500646 BRA0919 NP_700086.1 oxidoreductase, molybdopterin-binding, putative Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Formate dehydrogenase (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1014 araG from Brucella suis 1330 Brucella suis 1330 1165380 23500663 BRA0936 NP_700103.1 sugar ABC transporter, ATP-binding protein Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Transport (Delrue et al., 2004).

FUNCTION: L-arabinose transport (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages (Delrue et al., 2004).
14979322
1015 dacF from Brucella suis 1330 Brucella suis 1330 1165391 23500673 BRA0947 NP_700113.1 D-aminopeptidase Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan (Delrue et al., 2004).

FUNCTION: Peptidoglycan synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1016 cobW from Brucella suis 1330 Brucella suis 1330 1165431 23500711 BRA0987 NP_700151.1 cobalamin synthesis protein/P47K family protein Virulence factor MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis cobW gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). 12438693
1017 dppA from Brucella suis 1330 Brucella suis 1330 1165456 23500735 BRA1012 NP_700175.1 ABC transporter, periplasmic substrate-binding protein Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Transport (Delrue et al., 2004).

FUNCTION: Dipeptide uptake (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1018 znuA from Brucella suis 1330 Brucella suis 1330 1165575 23500837 BRA1122 NP_700277.1 zinc ABC transporter, periplasmic zinc-binding protein Virulence factor MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells (Kim et al., 2003). High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth (Kim et al., 2003). 12761078
1019 znuC from Brucella suis 1330 Brucella suis 1330 1165576 23500838 BRA1123 NP_700278.1 zinc ABC transporter, ATP-binding protein Virulence factor FUNCTIONAL GROUP: Metal acquisition (Delrue et al., 2004).

FUNCTION: Zn2+ uptake (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1020 flgE from Brucella suis 1330 Brucella suis 1330 1165592 23500854 BRA1139 NP_700294.1 flagellar hook protein FlgE Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (Delrue et al., 2004).

FUNCTION: Hook (Delrue et al., 2004).

SIMILARITY: Belongs to the flagella basal body rod proteins family(UniProt: Q8FUS9).

MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (Delrue et al., 2004).
14979322
1021 motB from Brucella suis 1330 Brucella from Brucella suis 1330 1165597 23500858 BRA1144 NP_700298.1 flagellar motor protein MotB Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (Delrue et al., 2004).

FUNCTION: Flagellar motor (Delrue et al., 2004).

MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (Delrue et al., 2004).
14979322
1022 fliF from Brucella suis 1330 Brucella suis 1330 1165599 23500860 BRA1146 NP_700300.1 flagellar MS-ring protein Virulence factor FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(UniProt: Q8FUS3).

SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(UniProt: Q8FUS3).

SUBCELLULAR LOCATION: Inner membrane; multi-pass membrane protein (By similarity)(UniProt: Q8FUS3).

SIMILARITY: Belongs to the fliF family(UniProt: Q8FUS3).

MUTATION: fliF is a gene potentially coding for the MS ring, a basal component of the flagellar system. Its mutant through signature- tagged mutagenesis is attenuated in vivo. It implicate a role for flagella in virulenc (Lestrate et al., 2003).
14638795
1023 rpsA from Brucella suis 1330 Brucella suis 1330 1165684 23500942 BR0027 NP_697069.1 30S ribosomal protein S1 Virulence factor MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis (Foulongne et al., 2000). 10678941
1024 pheA from Brucella suis 1330 Brucella suis 1330 1165694 23500952 BR0037 NP_697079.1 prephenate dehydratase Virulence factor MUTATION: The product of pheA gene is specifically dedicated to the biosynthesis of phenylalanine. The B. abortus pheA mutant with mini-Tn5 disruption displays nutritional defects in vitro. Experimental findings with the B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not. The pheA::miniTn5 mutant displayed attenuation in macrophages but not in mice (Alcantara et al., 2004). 15271960
1025 pgm from Brucella suis 1330 Brucella suis 1330 1165715 23500973 BR0058 NP_697100.1 phosphoglucomutase Virulence factor MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells (Ugalde et al., 2000).

B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro (Ugalde et al., 2000).
10992476
1026 ilvD from Brucella suis 1330 Brucella suis 1330 1165756 23501013 BR0099 NP_697140.1 dihydroxy-acid dehydratase Virulence factor CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(UniProt: Q8G353).

COFACTOR: Binds 1 4Fe-4S cluster (Potential)(UniProt: Q8G353).

PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-isoleucine from 2-oxobutanoate: step 3(UniProt: Q8G353).

PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from pyruvate: step 3(UniProt: Q8G353).

SIMILARITY: Belongs to the ilvD/edd family(UniProt: Q8G353).

MUTATION: Of those B abortus mutants with mini-Tn5 insertions in genes predicted to be involved in amino acid biosynthesis and transport, only the ilvD mutant, displayed attenuation in both macrophages and mice. The othre two amino acid biosynthesis mutants [trpB::miniTn5 and pheA::miniTn5] displayed wild-type virulence in mice but attenuated inside macrophages. The studies with B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not (Alcantara et al., 2004).
15271960
1027 ndvB from Brucella suis 1330 Brucella suis 1330 1165768 23501025 BR0111 NP_697152.1 cyclic beta 1-2 glucan synthetase Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: Synthesis of cyclic ( (Delrue et al., 2004).

MUTATION: Attenuated in Mice, HeLa (Delrue et al., 2004).
14979322
1028 glnD from Brucella suis 1330 Brucella suis 1330 1165801 23501056 BR0144 NP_697183.1 PII uridylyl-transferase Virulence factor FUNCTION: Modifies, by uridylylation or deuridylylation the PII (glnB) regulatory protein (By similarity)(UniProt: Q8G312).

CATALYTIC ACTIVITY: UTP + [protein-PII] = diphosphate + uridylyl-[protein-PII](UniProt: Q8G312).

SIMILARITY: Belongs to the glnD family(UniProt: Q8G312).

MUTATION: glnD encodes for a uridylyl transferase which is the primary sensor of nitrogen. The glnD mutant via signature-tagged transposon mutagenesis is attenuated in THP1 macrophages and HeLa cells. It supports the hypothesis that the concentration of glutamine in host cells is critical for the intracellular survival of Brucella (Foulongne et al., 2000).
10678941
1029 cysI from Brucella suis 1330 Brucella suis 1330 1165838 23501092 BR0181 NP_697219.1 sulfite reductase (NADPH) hemoprotein beta-component Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Sulfite reductate (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, but not in HeLa (Delrue et al., 2004).
14979322
1030 metH from Brucella suis 1330 Brucella suis 1330 1165845 23501099 BR0188 NP_697226.1 B12-dependent methionine synthase Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Met. synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1031 malK from Brucella suis 1330 Brucella suis 1330 1165896 23501145 BR0238 NP_697272.1 sugar ABC transporter, ATP-binding protein Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Transport (Delrue et al., 2004).

FUNCTION: Maltose transport (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, but not in HeLa (Delrue et al., 2004).
14979322
1032 hisD from Brucella suis 1330 Brucella suis 1330 1165911 23501159 BR0252 NP_697286.1 histidinol dehydrogenase Virulence factor FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(UniProt: Q8G2R2).

CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(UniProt: Q8G2R2).

COFACTOR: Binds 1 zinc ion per subunit (By similarity)(UniProt: Q8G2R2).

PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 9 [final step](UniProt: Q8G2R2).

SIMILARITY: Belongs to the histidinol dehydrogenase family(UniProt: Q8G2R2).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis hisD gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
12438693
1033 pgi from Brucella suis 1330 Brucella suis 1330 1165946 23501192 BR0285 NP_697319.1 glucose-6-phosphate isomerase Virulence factor CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(UniProt: Q8G2N3).

PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 2(UniProt: Q8G2N3).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G2N3).

SIMILARITY: Belongs to the GPI family(UniProt: Q8G2N3).

MUTATION: B. suis pgi is a gene identified by signature-tagged mutagenesis. The mutant is attenuated inside THP1 macrophages. The mutation of the pgi gene could also affect the biosynthesis of the bacterial peptidoglycan (Foulongne et al., 2000).
10678941
1034 pyrD from Brucella suis 1330 Brucella suis 1330 1165972 23501218 BR0311 NP_697345.1 dihydroorotate dehydrogenase 2 Virulence factor MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth (Kim et al., 2003). 12761078
1035 vsrB from Brucella suis 1330 Brucella suis 1330 1165977 23501223 BR0316 NP_697350.1 sensor histidine kinase/response regulator Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Histidine kinase (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1036 bacA from Brucella suis 1330 Brucella suis 1330 1166033 23501276 BR0372 NP_697403.1 transport protein Virulence factor MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain (LeVier et al., 2000). R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis (LeVier et al., 2000). The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria(LeVier et al., 2000). 10741969
1037 purD from Brucella suis 1330 Brucella suis 1330 1166075 23501317 BR0414 NP_697444.1 phosphoribosylamine--glycine ligase Virulence factor CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(UniProt: Q8G2B1).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; N(1)-(5-phospho-D-ribosyl)glycinamide from 5-phospho-alpha-D-ribose 1-diphosphate: step 2(UniProt: Q8G2B1).

PATHWAY: Context: Purine biosynthesis(UniProt: Q8G2B1).

SIMILARITY: Belongs to the GARS family(UniProt: Q8G2B1).

SIMILARITY: Contains 1 ATP-grasp domain(UniProt: Q8G2B1).

MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages (Alcantara et al., 2004).

Like the purE mutant, a purD::Tn10 mutant has reduced survival in murine macrophages and reduced virulence in mice (Alcantara et al., 2004).
15271960
1038 aroC from Brucella suis 1330 Brucella suis 1330 1166089 23501329 BR0428 NP_697456.1 chorismate synthase Virulence factor CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(UniProt: P63608).

COFACTOR: Reduced flavin (By similarity)(UniProt: P63608).

PATHWAY: Metabolic intermediate biosynthesis; chorismate biosynthesis; chorismate from D-erythrose 4-phosphate and PEP: step 7 [final step](UniProt: P63608).

PATHWAY: Context: Aromatic amino acids biosynthesis(UniProt: P63608).

SUBUNIT: Homotetramer (By similarity)(UniProt: P63608).

SIMILARITY: Belongs to the chorismate synthase family(UniProt: P63608).

MUTATION: The cloned aroC gene complements Escherichia coli and Salmonella enterica serovar Typhimurium aroC mutants. A B suis aroC mutant was found to be unable to grow in a defined medium without aromatic compounds. The mutant was highly attenuated in it issue culture (THP1 macrophages and HeLa cells) and murine virulence models (Foulongne et al., 2001).
11119550
1039 exsA from Brucella suis 1330 Brucella suis 1330 1166103 23501343 BR0442 NP_697470.1 ABC transporter, ATP-binding/permease protein Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Transport (Delrue et al., 2004).

FUNCTION: ABC transporter (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1040 purF from Brucella suis 1330 Brucella suis 1330 1166107 23501347 BR0446 NP_697474.1 amidophosphoribosyltransferase Virulence factor MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth (Kim et al., 2003). 12761078
1041 tldD from Brucella suis 1330 Brucella suis 1330 1166126 23501366 BR0465 NP_697493.1 tldD protein, putative Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation (Delrue et al., 2004).

FUNCTION: Putative modulator of DNA gyrase (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1042 thrC from Brucella suis 1330 Brucella suis 1330 1166145 23501385 BR0484 NP_697512.1 threonine synthase Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Thre. Synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1043 dsbA from Brucella suis 1330 Brucella suis 1330 1166157 23501397 BR0496 NP_697524.1 twin-arginine translocation signal domain protein Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Disulfide bond formation protein (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1044 wbpL from Brucella suis 1330 Brucella suis 1330 1166172 23501411 BR0511 NP_697538.1 glycosyl transferase, group 4 family protein Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages (Delrue et al., 2004).
14979322
1045 wbkB Brucella suis 1330 1166180 23501413 BR0518 AE014291 NP_697540 wbkB protein Virulence factor MUTATION: No function has been assigned to the B. melitensis 16M wbkB gene either by homology search or functionally, because deletion of wbkB did not interfere with the O-antigen structure (Godfroid et al., 2000). 11081580
1046 rfbD from Brucella suis 1330 Brucella suis 1330 1166182 23501415 BR0520 NP_697542.1 O-antigen export system permease protein RfbD Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages (Delrue et al., 2004).
14979322
1047 perA from Brucella suis 1330 Brucella suis 1330 1166183 23501416 BR0521 NP_697543.1 perosamine synthase, putative Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1048 gmd from Brucella suis 1330 Brucella suis 1330 1166184 23501417 BR0522 NP_697544.1 GDP-mannose 4,6-dehydratase Virulence factor MUTATION: gmd may be involved in perosamine synthesis. It has been shown to be in LPS synthesis since its B. melitensis mutation induces rough phenotype (Moriyón et al., 2004). 15099501
1049 wbkA from Brucella suis 1330 Brucella suis 1330 1166191 23501421 BR0529 NP_697548.1 mannosyltransferase, putative Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1050 pmm from Brucella suis 1330 Brucella suis 1330 1166199 23501426 BR0537 NP_697553.1 phosphomannomutase, putative Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1051 wbpZ from Brucella suis 1330 Brucella suis 1330 1166202 23501429 BR0540 NP_697556.1 glycosyl transferase, group 1 family protein Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages (Delrue et al., 2004).
14979322
1052 feuP from Brucella suis 1330 Brucella suis 1330 1166266 23501491 BR0604 NP_697618.1 DNA-binding response regulator Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Response regulator (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages (Delrue et al., 2004).
14979322
1053 feuQ from Brucella suis 1330 Brucella suis 1330 1166267 23501492 BR0605 NP_697619.1 sensor histidine kinase Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Histidine kinase (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1054 htrA from Brucella suis 1330 Brucella suis 1330 1166273 23501498 BR0611 NP_697625.1 serine protease Virulence factor FUNCTIONAL GROUP: Stress proteins/Chaperones (Kohler et al., 2002).

FUNCTION: Protease (Kohler et al., 2002).

MUTATION: Attenuated in "Goat", Macrophages, but not in Mice (Kohler et al., 2002).
12438693
1055 lpsA from Brucella suis 1330 Brucella suis 1330 1166277 23501502 BR0615 NP_697629.1 hypothetical protein Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: putative glycosyltranferase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1056 pepN from Brucella suis 1330 Brucella suis 1330 1166279 23501504 BR0617 NP_697631.1 aminopeptidase N Virulence factor MUTATION: A single mutation of PepN leads to a significant decrease in the growth rate, thus PepN seems to play a more prominent role than do the other proteases (Contreras-Rodriguez et al., 2003). 12933870
1057 spotT from Brucella suis 1330 Brucella suis 1330 1166315 23501539 BR0652 NP_697666.1 RelA/SpoT family protein Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: ppGpp synthetase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1058 omp25 from Brucella suis 1330 Brucella suis 1330 1166364 23501588 BR0701 NP_697715.1 outer-membrane protein Omp25 Virulence factor SUBCELLULAR LOCATION: Outer membrane(UniProt: Q45689).

SIMILARITY: Belongs to the omp25/ropB family(UniProt: Q45689).

MUTATION: In contrast to WT B suis or Deltaomp31 B suis, Deltaomp25 B suis induced TNF-alpha production when phagocytosed by human macrophages. So Omp25 of B suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages (Jubier-Maurin et al., 2001).

To determine the role of Omp25 in virulence, mutants were created with Brucella abortus (BA25), Brucella melitensis (BM25), and Brucella ovis (BO25) which contain disruptions in the omp25 gene (Deltaomp25 mutants). BALBc mice infected with B abortus BA25 or B melitensis BM25 showed a significant decrease in mean CFUspleen at 18 and 4 weeks post-infection, respectively, when compared to the virulent parental strain. Mice infected with B ovis BO25 had significantly lower mean CFUspleen counts from 1 to 8 weeks post-infection, at which point the mutant was cleared from the spleens. Murine vaccination with either BM25 or the current caprine vaccine B melitensis strain Rev.1 resulted in more than a 2log (10) reduction in bacterial load following challenge with virulent B melitensis. Vaccination of mice with the B ovis mutant resulted in clearance of the challenge strain and provided 2.5log (10) greater protection against virulent B ovis than vaccine strain Rev.1. Based on these data, the B melitensis and B ovis Deltaomp25 mutants are interesting vaccine candidates that are currently under study in our laboratory for their safety and efficacy in small ruminants (Jubier-Maurin et al., 2001).

Although they are slightly attenuated, B abortus omp25 and omp22 mutants do not show the high level of attenuation and sensitivity to bactericidal peptides displayed by the bvrS and bvrR mutants (Jubier-Maurin et al., 2001). B abortus mutants carrying Omp25 deletions do not show enrichment of underacylated LPS (Jubier-Maurin et al., 2001).

Brucella spp. omp25 deletion mutants are attenuated in mice, cattle and goats, showing the involvement of Brucella spp. Omp25 in virulence (Jubier-Maurin et al., 2001).
11447156
1059 purN from Brucella suis 1330 Brucella suis 1330 1166372 161486698 BR0709 NP_697723.2 phosphoribosylglycinamide formyltransferase Virulence factor MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study (Kim et al., 2003). 12761078
1060 purM from Brucella suis 1330 Brucella suis 1330 1166373 23501597 BR0710 NP_697724.1 phosphoribosylaminoimidazole synthetase Virulence factor CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(UniProt: Q8G1K5).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 2(UniProt: Q8G1K5).

PATHWAY: Context: Purine biosynthesis(UniProt: Q8G1K5).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G1K5).

SIMILARITY: Belongs to the AIR synthase family(UniProt: Q8G1K5).

MUTATION: B. abortus purM gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study (Kim et al., 2003).
12761078
1061 galE from Brucella suis 1330 Brucella suis 1330 1166378 23501602 BR0715 NP_697729.1 epimerase/dehydratase family protein, putative Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: UDP-glucose 4-epimerase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1062 glyA from Brucella suis 1330 Brucella suis 1330 1166430 23501652 BR0765 NP_697779.1 serine hydroxymethyltransferase Virulence factor FUNCTION: Interconversion of serine and glycine(UniProt: Q8G1F1).

CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(UniProt: Q8G1F1).

COFACTOR: Pyridoxal phosphate (By similarity)(UniProt: Q8G1F1).

PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(UniProt: Q8G1F1).

SUBUNIT: Homotetramer (By similarity)(UniProt: Q8G1F1).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G1F1).

SIMILARITY: Belongs to the SHMT family(UniProt: Q8G1F1).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
12438693
1063 purL from Brucella suis 1330 Brucella suis 1330 1166505 23501724 BR0837 NP_697851.1 phosphoribosylformylglycinamidine synthase II Virulence factor CATALYTIC ACTIVITY: ATP + N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H(2)O = ADP + phosphate + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine + L-glutamate(UniProt: Q8G183).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 1(UniProt: Q8G183).

PATHWAY: Context: Purine biosynthesis(UniProt: Q8G183).

SUBUNIT: Heterodimer of two subunits, purQ and purL(UniProt: Q8G183).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G183).

SIMILARITY: Belongs to the FGAMS family(UniProt: Q8G183).

MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages (Alcantara et al., 2004). Studies with B melitensis purE and B abortus purL mutants, which are purine auxotrophs, and B suis aroC mutants, which can not synthesize aromatic amino acids, indicate that the brucellae also face signicant nutrient limitation during their prolonged residence in host macrophages (Alcantara et al., 2004).
15271960
1064 tig from Brucella suis 1330 Brucella suis 1330 1166567 23501784 BR0898 NP_697911.1 trigger factor Virulence factor FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(UniProt: Q8G129).

SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(UniProt: Q8G129).

SIMILARITY: Contains 1 PPIase FKBP-type domain(UniProt: Q8G129).

MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice (Lestrate et al., 2003).
14638795
1065 dsbA from Brucella suis 1330 Brucella suis 1330 1166578 23501795 BR0909 NP_697922.1 outer membrane protein, putative Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Disulfide bond formation protein (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1066 amiC from Brucella suis 1330 Brucella suis 1330 1166584 23501801 BR0915 NP_697928.1 N-acetylmuramoyl-L-alanine amidase, family 3 Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan (Delrue et al., 2004).

FUNCTION: Cell-wall hydrolysis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1067 nifS from Brucella suis 1330 Brucella suis 1330 1166599 23501814 BR0930 NP_697941.1 cysteine desulfurase, putative Virulence factor FUNCTIONAL GROUP: Nitrogen metabolism (Delrue et al., 2004).

FUNCTION: nitrogenase cofactor synthesis protein nifS (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1068 dsbA from Brucella suis 1330 Brucella suis 1330 1166602 23501817 BR0933 NP_697944.1 hypothetical protein Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Disulfide bond formation protein (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1069 artI from Brucella suis 1330 Brucella suis 1330 1166625 23501838 BR0955 NP_697965.1 amino acid ABC transporter, periplasmic amino acid-binding protein Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Transport (Delrue et al., 2004).

FUNCTION: Arginine transport system (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
14979322
1070 wbdA from Brucella suis 1330 Brucella suis 1330 1166655 23501863 BR0982 NP_697990.1 glycosyl transferase, group 1 family protein Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1071 glnA from Brucella suis 1330 Brucella suis 1330 1166677 23501884 BR1004 NP_698011.1 glutamine synthetase, type I Virulence factor MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). 12438693
1072 cysK from Brucella suis 1330 Brucella suis 1330 1166727 23501931 BR1053 NP_698058.1 cysteine synthase A Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Cys. synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1073 caiB from Brucella suis 1330 Brucella suis 1330 1166760 23501962 BR1084 NP_698089.1 CAIB/BAIF family protein Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: CAIB/BAIF family (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1074 uvrA from Brucella suis 1330 Brucella suis 1330 1166780 23501982 BR1104 NP_698109.1 excinuclease ABC subunit A Virulence factor FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(UniProt: Q8G0I9).

SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(UniProt: Q8G0I9).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G0I9).

SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(UniProt: Q8G0I9).

SIMILARITY: Contains 2 ABC transporter domains(UniProt: Q8G0I9).

MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants (Roux et al., 2006).
16816190
1075 lon from Brucella suis 1330 Brucella suis 1330 1166782 23501984 BR1106 NP_698111.1 ATP-dependent protease La Virulence factor FUNCTION: Degrades short-lived regulatory and abnormal proteins in presence of ATP. Hydrolyzes two ATPs for each peptide bond cleaved in the protein substrate (By similarity)(UniProt: Q8G0I7).

CATALYTIC ACTIVITY: Hydrolysis of proteins in presence of ATP(UniProt: Q8G0I7).

SUBUNIT: Homotetramer (By similarity)(UniProt: Q8G0I7).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G0I7).

SIMILARITY: Belongs to the peptidase S16 family(UniProt: Q8G0I7).

SIMILARITY: Contains 1 Lon domain(UniProt: Q8G0I7).

MUTATION: In contrast to the parent strain, the Brucella abortus lon mutant, was impaired in its capacity to form isolated colonies on solid medium at 41 degrees C and displayed an increased sensitivity to killing by puromycin and H2O2. Brucella abortus Lon homologue functions as a stress response protease that is required for wild-type virulence during the initial stages of infection in the mouse model, but is not essential for the establishment and maintenance of chronic infection in this host (Robertson et al., 2000).

Both single lon or clpA mutations had comparable effects on growth inhibition, suggesting that the concerned proteases Lon and ClpAP both degrade a number of specific proteins, but are also both involved in general degradation of abnormal proteins. Compared to the single mutants, the double mutant lon clpA was highly sensitive to canavanine. One possible explanation for this observation is that both proteases can substitute for each other to a large extent during bacterial growth. Hence, simultaneous inactivation or decrease in activation of both proteases, either by direct mutation or by elimination of the regulatory component ClpA, strongly increased growth inhibition (Robertson et al., 2000).
10672180
1076 hfq from Brucella suis 1330 Brucella suis 1330 1166787 23501989 BR1111 NP_698116.1 RNA-binding protein Hfq Virulence factor FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(UniProt: P0A3G8).

SIMILARITY: Belongs to the hfq family(UniProt: P0A3G8).

MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source(Sonnleitner et al., 2003).

hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages (Sonnleitner et al., 2003).

In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication (Sonnleitner et al., 2003).

A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type (Sonnleitner et al., 2003).
14521880
1077 ntrY from Brucella suis 1330 Brucella suis 1330 1166792 23501994 BR1116 NP_698121.1 nitrogen regulation protein NtrY Virulence factor MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype (Foulongne et al., 2000). 10678941
1078 ntrC from Brucella suis 1330 Brucella suis 1330 1166793 23501995 BR1117 NP_698122.1 nitrogen regulation protein NtrC Virulence factor MUTATION: ntrC encodes for a response regulator subfamily (NtrC). A B suis ntrC isogenic mutant was constructed which showed no significant differences in growth rates compared to the wild-type strain when grown at different temperatures in vitro. However, the mutant exhibited a reduction in metabolic activity in the presence of many amino acids. The mutation did not affect survival or multiplication of B suis in macrophages, but during the initial stages of infection in the murine brucellosis model, the ntrC mutant showed a reduced ability to multiply rapidly in splenic tissue (Dorrell et al., 1999). 10373105
1079 ppiD from Brucella suis 1330 Brucella suis 1330 1166815 23502017 BR1139 NP_698144.1 rotamase family protein Virulence factor FUNCTIONAL GROUP: Stress proteins/Chaperones (Delrue et al., 2004).

FUNCTION: Rotamase D (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1080 uppS from Brucella suis 1330 Brucella suis 1330 1166834 23502036 BR1158 NP_698163.1 undecaprenyl diphosphate synthase Virulence factor FUNCTION: Generates undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate (IPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide (By similarity)(UniProt: Q8G0D9).

CATALYTIC ACTIVITY: Di-trans,poly-cis-decaprenyl diphosphate + isopentenyl diphosphate = diphosphate + di-trans,poly-cis-undecaprenyl diphosphate(UniProt: Q8G0D9).

COFACTOR: Magnesium (By similarity)(UniProt: Q8G0D9).

SUBUNIT: Homodimer (By similarity)(UniProt: Q8G0D9).

SIMILARITY: Belongs to the UPP synthetase family(UniProt: Q8G0D9).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis uppS gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
12438693
1081 recA from Brucella suis 1330 Brucella suis 1330 1166878 23502079 BR1202 NP_698206.1 recombinase A Virulence factor FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(UniProt: P65976).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: P65976).

SIMILARITY: Belongs to the recA family(UniProt: P65976).

MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice (Halling, 2002).

The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persistence phase (Halling, 2002).

12414170
1082 rpoA from Brucella suis 1330 Brucella suis 1330 1166885 23502086 BR1209 NP_698213.1 DNA-directed RNA polymerase subunit alpha Virulence factor FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(UniProt: Q8G094).

CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(UniProt: Q8G094).

SUBUNIT: Homodimer. The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription (By similarity)(UniProt: Q8G094).

DOMAIN: The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity)(UniProt: Q8G094).

SIMILARITY: Belongs to the RNA polymerase alpha chain family(UniProt: Q8G094).

MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress (Lestrate et al., 2003).
14638795
1083 gloA from Brucella suis 1330 Brucella suis 1330 1166947 23502144 BR1268 NP_698271.1 lactoylglutathione lyase Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
14979322
1084 cobB from Brucella suis 1330 Brucella suis 1330 1166977 23502172 BR1296 NP_698299.1 cobyrinic acid a,c-diamide synthase Virulence factor FUNCTION: Responsible for the amidation of carboxylic groups at position A and C of either cobyrinic acid or hydrogenobrynic acid. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolyzed for each amidation (By similarity)(UniProt: Q8G020).

PATHWAY: Cobalamin biosynthesis(UniProt: Q8G020).

SIMILARITY: Belongs to the cobB/cobQ family. CobB subfamily(UniProt: Q8G020).

MUTATION: 1,152 signature-tagged mutagenesis mutants of Brucella melitensis 16M were screened in a mouse model of infection. 36 of them to be attenuated in vivo. cobB is one of them (Lestrate et al., 2003).
14638795
1085 aspB from Brucella suis 1330 Brucella suis 1330 1167060 23502249 BR1378 NP_698376.1 aminotransferase, class I Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: Aminotransferase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1086 ilvC from Brucella suis 1330 Brucella suis 1330 1167062 23502251 BR1380 NP_698378.1 ketol-acid reductoisomerase Virulence factor CATALYTIC ACTIVITY: (R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH(UniProt: Q8FZU1).

CATALYTIC ACTIVITY: (2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-hydroxy-2-ethyl-3-oxobutanoate + NADPH(UniProt: Q8FZU1).

PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-isoleucine from 2-oxobutanoate: step 2(UniProt: Q8FZU1).

PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from pyruvate: step 2(UniProt: Q8FZU1).

SIMILARITY: Belongs to the ketol-acid reductoisomerase family(UniProt: Q8FZU1).

MUTATION: ilvC is one of the 37 mutants with virulene defect, screened out from the signature- tagged miniTn5 library (Lestrate et al., 2003).
14638795
1087 miaA from Brucella suis 1330 Brucella suis 1330 1167072 23502261 BR1390 NP_698388.1 tRNA delta(2)-isopentenylpyrophosphate transferase Virulence factor FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(UniProt: Q8CY40).

CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(UniProt: Q8CY40).

SIMILARITY: Belongs to the IPP transferase family(UniProt: Q8CY40).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
12438693
1088 serB from Brucella suis 1330 Brucella suis 1330 1167073 23502262 BR1391 NP_698389.1 phosphoserine phosphatase Virulence factor MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis serB gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). 12438693
1089 pncA from Brucella suis 1330 Brucella suis 1330 1167146 23502333 BR1464 NP_698460.1 pyrazinamidase/nicotinamidase Virulence factor MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells (Kim et al., 2003). Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages (Kim et al., 2003). The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks (Kim et al., 2003). It indicates that the mutant has reduced virulence in mice. 12761078
1090 pncA from Brucella suis 1330 Brucella suis 1330 1167147 23502334 BR1465 NP_698461.1 hypothetical protein Virulence factor MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells (Kim et al., 2003). Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages (Kim et al., 2004). The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks (Kim et al., 2004). It indicates that the mutant has reduced virulence in mice. 12761078 15135535
1091 aspC from Brucella suis 1330 Brucella suis 1330 1167178 23502364 BR1495 NP_698491.1 aspartate aminotransferase Virulence factor MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth (Kim et al., 2003). 12761078
1092 lysR from Brucella suis 1330 Brucella suis 1330 1167181 23502367 BR1498 NP_698494.1 transcriptional regulator, LysR family Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (Delrue et al., 2004).

FUNCTION: Transcriptional regulator (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
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1093 pth from Brucella suis 1330 Brucella suis 1330 1167219 23502404 BR1536 NP_698531.1 peptidyl-tRNA hydrolase Virulence factor FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(UniProt: P65864).

CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(UniProt: P65864).

SUBUNIT: Monomer (By similarity)(UniProt: P65864).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: P65864).

SIMILARITY: Belongs to the PTH family(UniProt: P65864).

MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed (Danese et al., 2004).
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1094 leuA from Brucella suis 1330 Brucella suis 1330 1167249 161486694 BR1566 NP_698557.2 2-isopropylmalate synthase Virulence factor FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(UniProt: Q8FZC4).

CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(UniProt: Q8FZC4).

PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 1(UniProt: Q8FZC4).

SUBUNIT: Homotetramer (By similarity)(UniProt: Q8FZC4).

SIMILARITY: Belongs to the alpha-IPM synthetase/homocitrate synthase family. LeuA type 2 subfamily(UniProt: Q8FZC4).

MUTATION: leuA is a B. suis gene identified by signature-tagged mutagenesis. It is attenuated inside THP1 macrophage cell line.
1095 dsbB from Brucella suis 1330 Brucella suis 1330 1167334 23502502 BR1642 NP_698629.1 disulfide bond formation protein B, putative Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Disulfide bond formation protein (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages (Delrue et al., 2004).
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1096 alkA from Brucella suis 1330 Brucella suis 1330 1167338 23502506 BR1646 NP_698633.1 base-excision DNA repair protein Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Repair (Delrue et al., 2004).

FUNCTION: HhH-GPD superfamily base excision DNA repair (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
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1097 macA from Brucella suis 1330 Brucella suis 1330 1167364 23502529 BR1671 NP_698656.1 HlyD family secretion protein Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (Delrue et al., 2004).

FUNCTION: Macrolide efflux (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
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1098 dut from Brucella suis 1330 Brucella suis 1330 1167368 23502533 BR1675 NP_698660.1 deoxyuridine 5'-triphosphate nucleotidohydrolase Virulence factor FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(UniProt: P64005).

CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(UniProt: P64005).

PATHWAY: De novo synthesis of thymidylate(UniProt: P64005).

SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). the dUTPase family(UniProt: P64005).
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1099 ansC from Brucella suis 1330 Brucella suis 1330 1167369 23502534 BR1676 NP_698661.1 transcriptional regulator, AsnC family Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (Delrue et al., 2004).

FUNCTION: Transcriptional regulator (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
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1100 purE from Brucella suis 1330 Brucella suis 1330 1167437 23502601 BR1744 NP_698728.1 phosphoribosylaminoimidazole carboxylase, catalytic subunit Virulence factor FUNCTION: This subunit can alone transform AIR to CAIR, but in association with purK, which possesses an ATPase activity, an enzyme complex is produced which is capable of converting AIR to CAIR efficiently under physiological condition (By similarity)(UniProt: Q8FYW3).

CATALYTIC ACTIVITY: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO(2)(UniProt: Q8FYW3).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 3(UniProt: Q8FYW3).

PATHWAY: Context: Purine biosynthesis(UniProt: Q8FYW3).

SUBUNIT: Homooctamer (By similarity)(UniProt: Q8FYW3).

SIMILARITY: Belongs to the AIR carboxylase family(UniProt: Q8FYW3).

MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages (Alcantara et al., 2004). The purE mutant has reduced survival in murine macrophages and reduced virulence in mice (Alcantara et al., 2004).

A purE gene deletion mutant (purE201) of B melitensis was constructed as a potentially useful vaccine for humans and animals. At necropsy, bacteria were present in mammary lymph nodes or spleen of 33 of goats given virulent 16M but in none of goats given the purE mutant. The purE mutation of B melitensis 16M was stable and that the vaccine could be differentiated from wild-type strains by hybridization, purine auxotrophy, and kanamycin resistance. Mice clear the identical purE mutant strain from their spleens in only 8 weeks but remain infected with B. melitensis 16M for at least 3 months (Alcantara et al., 2004).
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1101 pyc from Brucella suis 1330 Brucella suis 1330 1167474 23502636 BR1781 NP_698763.1 pyruvate carboxylase Virulence factor MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages (Foulongne et al., 2000). 10678941
1102 livH from Brucella suis 1330 Brucella suis 1330 1167484 23502645 BR1791 NP_698772.1 branched-chain amino acid ABC transporter, permease protein Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Transport (Delrue et al., 2004).

FUNCTION: Branched as transport system (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
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1103 purH from Brucella suis 1330 Brucella suis 1330 1167509 23502669 BR1816 NP_698796.1 bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase Virulence factor CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(UniProt: P67540).

CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(UniProt: P67540).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (10-formyl THF route): single step(UniProt: P67540).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide: single step [final step](UniProt: P67540).

PATHWAY: Context: Purine biosynthesis(UniProt: P67540).

DOMAIN: The IMP cyclohydrolase activity resides in the N-terminal region (By similarity)(UniProt: P67540).

SIMILARITY: Belongs to the purH family(UniProt: P67540).

MUTATION: B. abortus mutant with mini-Tn5-disrupted purH displays nutritional defects in vitro (Alcantara et al., 2004).
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1104 leuC from Brucella suis 1330 Brucella suis 1330 1167606 23502757 BR1906 NP_698884.1 isopropylmalate isomerase large subunit Virulence factor FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(UniProt: Q8FYG9).

CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(UniProt: Q8FYG9).

CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(UniProt: Q8FYG9).

COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(UniProt: Q8FYG9).

PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 2(UniProt: Q8FYG9).

SUBUNIT: Heterodimer of leuC and leuD (By similarity)(UniProt: Q8FYG9).

SIMILARITY: Belongs to the aconitase/IPM isomerase family. LeuC type 1 subfamily(UniProt: Q8FYG9).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis leuC gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
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1105 rplS from Brucella suis 1330 Brucella suis 1330 1167607 23502758 BR1907 NP_698885.1 50S ribosomal protein L19 Virulence factor FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity)(UniProt: P66079).

SIMILARITY: Belongs to the ribosomal protein L19P family(UniProt: P66079).

MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro (Alcantara et al., 2004).
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1106 omp19 from Brucella suis 1330 Brucella suis 1330 1167630 23502780 BR1930 NP_698907.1 lipoprotein Omp19 Virulence factor SUBCELLULAR LOCATION: Outer membrane; lipid-anchor(UniProt: P0A3P2).

MISCELLANEOUS: Elicits an immune response in humans, mice, sheep and goats infected with B.melitensis or B.abortus, but not in B.abortus-infected cattle(UniProt: P0A3P2).

SIMILARITY: Belongs to the rhizobiaceae omp19 lipoprotein family(UniProt: P0A3P2).

MUTATION: Omp19 is an immunoreactive outer membrane lipoprotein. Significantly fewer brucellae were recovered from the spleens of mice infected with the omp19 mutant than from those of mice infected with the parent strain at 4 and 8 weeks postinfection. The omp19 mutant exhibited an increase in sensitivity to the polycation polymyxin B and to sodium deoxycholate. These results indicate that inactivation of the omp19 gene alters the outer membrane properties of B abortus (Tibor et al., 2002).
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1107 cysK from Brucella suis 1330 Brucella suis 1330 1167668 0 BR1967 - pseudo Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Cys. synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
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1108 lysA from Brucella suis 1330 Brucella suis 1330 1167684 23502831 BR1983 NP_698958.1 diaminopimelate decarboxylase Virulence factor MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). 12438693
1109 hpt from Brucella suis 1330 Brucella suis 1330 1167686 23502833 BR1985 NP_698960.1 hypoxanthine-guanine phosphoribosyltransferase Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Purines synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
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1110 hisC from Brucella suis 1330 Brucella suis 1330 1167688 23502835 BR1987 NP_698962.1 histidinol-phosphate aminotransferase Virulence factor CATALYTIC ACTIVITY: L-histidinol phosphate + 2-oxoglutarate = 3-(imidazol-4-yl)-2-oxopropyl phosphate + L-glutamate(UniProt: Q8FY98).

COFACTOR: Pyridoxal phosphate (By similarity)(UniProt: Q8FY98).

PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 7(UniProt: Q8FY98).

SUBUNIT: Homodimer (By similarity)(UniProt: Q8FY98).

SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family. Histidinol-phosphate aminotransferase subfamily(UniProt: Q8FY98).

MUTATION: hisC encodes for histidinol phosphate transaminase. Brucella hisC mutant showed very little reduction in number by 2 weeks post-inoculation, but was reduced by 8 weeks.
1111 hisF from Brucella suis 1330 Brucella suis 1330 1167788 23502933 BR2085 NP_699060.1 imidazole glycerol phosphate synthase subunit HisF Virulence factor FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(UniProt: Q8FY07).

CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(UniProt: Q8FY07).

PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 5(UniProt: Q8FY07).

SUBUNIT: Heterodimer of hisH and hisF (By similarity)(UniProt: Q8FY07).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8FY07).

SIMILARITY: Belongs to the hisA/hisF family(UniProt: Q8FY07).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis hisF gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
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1112 bvrR from Brucella suis 1330 Brucella suis 1330 1167793 23502938 BR2090 NP_699065.1 DNA-binding response regulator BvrR, putative Virulence factor MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly (Guzman-Verri et al., 2002).

Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism (Guzman-Verri et al., 2002).

In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments (Guzman-Verri et al., 2002).

B abortus bvrS bvrR mutants display reduced invasiveness and virulence (Guzman-Verri et al., 2002).

Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact (Guzman-Verri et al., 2002).

Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments (Guzman-Verri et al., 2002).

BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly (Guzman-Verri et al., 2002).
12218183
1113 bvrS from Brucella suis 1330 Brucella suis 1330 1167794 23502939 BR2091 NP_699066.1 sensor histidine kinase BvrS, putative Virulence factor MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly (Guzman-Verri et al., 2002).

Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism (Guzman-Verri et al., 2002).

In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments (Guzman-Verri et al., 2002).

B abortus bvrS bvrR mutants display reduced invasiveness and virulence (Guzman-Verri et al., 2002).

Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact (Guzman-Verri et al., 2002).

Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments (Guzman-Verri et al., 2002).

BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly (Guzman-Verri et al., 2002).
12218183
1114 dnaK from Brucella suis 1330 Brucella suis 1330 1167828 23502973 BR2125 NP_699100.1 molecular chaperone DnaK Virulence factor FUNCTION: Acts as a chaperone (By similarity)(UniProt: Q8FXX2).

INDUCTION: By stress conditions e.g. heat shock (By similarity)(UniProt: Q8FXX2).

SIMILARITY: Belongs to the heat shock protein 70 family(UniProt: Q8FXX2).

MUTATION: The heat shock protein DnaK is essential for intramacrophagic replication of Brucella suis. The replacement of the stress-inducible, native dnaK promoter of B suis by the promoter of the constitutively expressed bla gene resulted in temperature-independent synthesis of DnaK. In contrast to a dnaK null mutant, this strain grew at 37 degrees C, with a thermal cutoff at 39 degrees C However, the constitutive dnaK mutant, which showed high sensitivity to H(2)O(2)-mediated stress , failed to multiply in murine macrophage-like cells and was rapidly eliminated in a mouse model of infection, adding strong arguments that stress-mediated and heat shock promoter-dependent induction of dnaK is a crucial event in the intracellular replication of B suis (Köhler et al., 2002).

Mutation studies indicated that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. Viability of the dnaK null mutant was also greatly affected at low pH. In infection experiments performed with both mutants at the reduced temperature of 30 degrees C, the dnaK mutant of B suis survived but failed to multiply within U937 cells, whereas the wild-type strain and the dnaJ mutant multiplied normally. Complementation of the dnaK mutant with the cloned dnaK gene restored growth at 37 degrees C, increased resistance to acid pH, and increased intracellular multiplication (Köhler et al., 2002).
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1115 pmtA Brucella suis 1330 1167830 23502975 BR2127 AE014291 NP_699102 phospholipid N-methyltransferase Virulence factor MUTATION: The role of Phosphatidylcholine (PC) in Brucella abortus was examined by generating mutants in pcs (BApcs) and pmtA (BApmtA), which encode key enzymes of the two bacterial PC biosynthetic routes, the choline and methyl-transferase pathways. In rich medium, BApcs and the double mutant BApcspmtA but not BApmtA displayed reduced growth, increased phosphatidylethanolamine and no PC, showing that Pcs is essential for PC synthesis under these conditions. In minimal medium, the parental strain, BApcs and BApmtA showed reduced but significant amounts of PC suggesting that PmtA may also be functional Probing with phage Tb, antibiotics, polycations and serum demonstrated that all mutants had altered envelopes. In macrophages, BApcs and BApcspmtA showed reduced ability to evade fusion with lysosomes and establish a replication niche. In mice, BApcs showed attenuation only at early times after infection, BApmtA at later stages and BApcspmtA throughout. The results suggest that Pcs and PmtA have complementary roles in vivo related to nutrient availability and that PC and the membrane properties that depend on this typical eukaryotic phospholipid are essential for Brucella virulence (Conde-Alvarez et al., 2006). 16882035
1116 mutM from Brucella suis 1330 Brucella suis 1330 1167886 23503030 BR2183 NP_699157.1 formamidopyrimidine-DNA glycosylase Virulence factor FUNCTION: Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates (By similarity)(UniProt: Q8FXR6).

CATALYTIC ACTIVITY: Hydrolysis of DNA containing ring-opened N(7)-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine(UniProt: Q8FXR6).

CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate(UniProt: Q8FXR6).

COFACTOR: Binds 1 zinc ion per subunit (By similarity)(UniProt: Q8FXR6).

SUBUNIT: Monomer (By similarity)(UniProt: Q8FXR6).

SIMILARITY: Belongs to the FPG family(UniProt: Q8FXR6).

SIMILARITY: Contains 1 FPG-type zinc finger(UniProt: Q8FXR6).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
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1202 hpt from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1195794 17986366 BMEI0082 NP_539000.1 hypoxanthine-guanine phosphoribosyltransferase Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Purines synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
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1203 lysA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1195796 17986368 BMEI0084 NP_539002.1 DIAMINOPIMELATE DECARBOXYLASE Virulence factor MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). 12438693
1204 BMEI0085 Brucella 1195797 17986369 BMEI0085 NP_539003.1 hypothetical protein Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: Brucella orphan gene (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
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1205 omp19 from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1195847 17986419 BMEI0135 NP_539053.1 OUTER MEMBRANE LIPOPROTEIN Virulence factor SUBCELLULAR LOCATION: Outer membrane; lipid-anchor(UniProt: P0A3P2).

MISCELLANEOUS: Elicits an immune response in humans, mice, sheep and goats infected with B.melitensis or B.abortus, but not in B.abortus-infected cattle(UniProt: P0A3P2).

SIMILARITY: Belongs to the rhizobiaceae omp19 lipoprotein family(UniProt: P0A3P2).

MUTATION: Omp19 is an immunoreactive outer membrane lipoprotein. Significantly fewer brucellae were recovered from the spleens of mice infected with the omp19 mutant than from those of mice infected with the parent strain at 4 and 8 weeks postinfection. The omp19 mutant exhibited an increase in sensitivity to the polycation polymyxin B and to sodium deoxycholate. These results indicate that inactivation of the omp19 gene alters the outer membrane properties of B abortus (Tibor et al., 2002).
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1206 rplS from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1195868 17986440 BMEI0156 NP_539074.1 50S ribosomal protein L19 Virulence factor FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity)(UniProt: P66079).

SIMILARITY: Belongs to the ribosomal protein L19P family(UniProt: P66079).

MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro (Alcantara et al., 2004).
15271960
1207 leuC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1195869 17986441 BMEI0157 NP_539075.1 isopropylmalate isomerase large subunit Virulence factor FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(UniProt: Q8FYG9).

CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(UniProt: Q8FYG9).

CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(UniProt: Q8FYG9).

COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(UniProt: Q8FYG9).

PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 2(UniProt: Q8FYG9).

SUBUNIT: Heterodimer of leuC and leuD (By similarity)(UniProt: Q8FYG9).

SIMILARITY: Belongs to the aconitase/IPM isomerase family. LeuC type 1 subfamily(UniProt: Q8FYG9).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis leuC gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
12438693
1208 gntR4 Brucella 1195881 17986453 BMEI0169 NP_539087.1 TRANSCRIPTIONAL REGULATOR, GNTR FAMILY / AMINOTRANSFERASE CLASS-I Virulence factor FUNCTIONAL GROUP: gntR family (Haine et al., 2005).

MUTATION: Attenuated using plasmid-tagged mutagenesis method (Haine et al., 2005).
16113274
1209 pstP Brucella melitensis bv. 1 str. 16M 1195902 17986474 BMEI0190 NZ_GG703778 NP_539108 phosphoenolpyruvate-protein phosphotransferase PTSP Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (Delrue et al., 2004).

FUNCTION: Phosphoenolypruvate phosphotransferase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1210 purH from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1195945 17986517 BMEI0233 NP_539151.1 bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase Virulence factor CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(UniProt: P67540).

CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(UniProt: P67540).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (10-formyl THF route): single step(UniProt: P67540).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide: single step [final step](UniProt: P67540).

PATHWAY: Context: Purine biosynthesis(UniProt: P67540).

DOMAIN: The IMP cyclohydrolase activity resides in the N-terminal region (By similarity)(UniProt: P67540).

SIMILARITY: Belongs to the purH family(UniProt: P67540).

MUTATION: B. abortus mutant with mini-Tn5-disrupted purH displays nutritional defects in vitro (Alcantara et al., 2004).
15271960
1211 livH from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1195970 17986542 BMEI0258 NP_539176.1 HIGH-AFFINITY BRANCHED-CHAIN AMINO ACID TRANSPORT SYSTEM PERMEASE PROTEIN LIVH Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Transport (Delrue et al., 2004).

FUNCTION: Branched as transport system (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
14979322
1212 pyc from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1195978 17986550 BMEI0266 NP_539184.1 pyruvate carboxylase Virulence factor MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages (Foulongne et al., 2000). 10678941
1213 mosC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1195979 17986551 BMEI0267 NP_539185.1 MEMBRANE PROTEIN MOSC Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Transport (Delrue et al., 2004).

FUNCTION: Rhizopine transport (Delrue et al., 2004).

MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (Delrue et al., 2004).
14979322
1214 mgps Brucella melitensis bv. 1 str. 16M 1195987 17986559 BMEI0275 AE008917 NP_539193 ATP-dependent DNA helicase Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation (Delrue et al., 2004).

FUNCTION: RNA helicase family (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1215 purE from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196007 17986579 BMEI0296 NP_539213.1 PHOSPHORIBOSYLAMINOIMIDAZOLE CARBOXYLASE CATALYTIC SUBUNIT Virulence factor FUNCTION: This subunit can alone transform AIR to CAIR, but in association with purK, which possesses an ATPase activity, an enzyme complex is produced which is capable of converting AIR to CAIR efficiently under physiological condition (By similarity)(UniProt: Q8FYW3).

CATALYTIC ACTIVITY: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO(2)(UniProt: Q8FYW3).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 3(UniProt: Q8FYW3).

PATHWAY: Context: Purine biosynthesis(UniProt: Q8FYW3).

SUBUNIT: Homooctamer (By similarity)(UniProt: Q8FYW3).

SIMILARITY: Belongs to the AIR carboxylase family(UniProt: Q8FYW3).

MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages (Alcantara et al., 2004). The purE mutant has reduced survival in murine macrophages and reduced virulence in mice (Alcantara et al., 2004).

A purE gene deletion mutant (purE201) of B melitensis was constructed as a potentially useful vaccine for humans and animals. At necropsy, bacteria were present in mammary lymph nodes or spleen of 33 of goats given virulent 16M but in none of goats given the purE mutant. The purE mutation of B melitensis 16M was stable and that the vaccine could be differentiated from wild-type strains by hybridization, purine auxotrophy, and kanamycin resistance. Mice clear the identical purE mutant strain from their spleens in only 8 weeks but remain infected with B. melitensis 16M for at least 3 months (Alcantara et al., 2004).
15271960
1216 gntR2 Brucella melitensis bv. 1 str. 16M 1196016 17986588 BMEI0305 AE008917 NP_539222 DeoR family transcriptional regulator Virulence factor FUNCTIONAL GROUP: gntR family (Haine et al., 2005).

MUTATION: Attenuated in mice (Haine et al., 2005).
16113274
1217 gntR17 Brucella melitensis bv. 1 str. 16M 1196031 17986603 BMEI0320 AE008917 NP_539237 GntR family transcriptional regulator Virulence factor FUNCTIONAL GROUP: gntR family (Haine et al., 2005).

MUTATION: Attenuated in mice (Haine et al., 2005).
16113274
1218 ansC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196068 17986640 BMEI0357 NP_539274.1 TRANSCRIPTIONAL REGULATORY PROTEIN, ASNC FAMILY Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (Delrue et al., 2004).

FUNCTION: Transcriptional regulator (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1219 dut from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196069 17986641 BMEI0358 NP_539275.1 deoxyuridine 5'-triphosphate nucleotidohydrolase Virulence factor FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(UniProt: P64005).

CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(UniProt: P64005).

PATHWAY: De novo synthesis of thymidylate(UniProt: P64005).

SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). the dUTPase family(UniProt: P64005).
12438693
1220 macA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196070 17986642 BMEI0359 NP_539276.1 periplasmic component of efflux system Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (Delrue et al., 2004).

FUNCTION: Macrolide efflux (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1221 alkA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196093 17986665 BMEI0382 NP_539299.1 DNA-3-METHYLADENINE GLYCOSIDASE Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Repair (Delrue et al., 2004).

FUNCTION: HhH-GPD superfamily base excision DNA repair (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1222 dsbB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196095 17986667 BMEI0384 NP_539301.1 DISULFIDE BOND FORMATION PROTEIN B Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Disulfide bond formation protein (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages (Delrue et al., 2004).
14979322
1223 arsR6 Brucella melitensis bv. 1 str. 16M 1196141 17986713 BMEI0430 AE008917 NP_539347 nodulation protein NOLR Virulence factor FUNCTIONAL GROUP: ArsR family (Haine et al., 2005).

MUTATION: Attenuated in mice (Haine et al., 2005).
16113274
1224 dppA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196144 17986716 BMEI0433 NP_539350.1 PERIPLASMIC DIPEPTIDE TRANSPORT PROTEIN PRECURSOR Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Transport (Delrue et al., 2004).

FUNCTION: Dipeptide uptake (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1225 leuA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196162 17986734 BMEI0451 NP_539368.1 2-isopropylmalate synthase Virulence factor FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(UniProt: Q8FZC4).

CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(UniProt: Q8FZC4).

PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 1(UniProt: Q8FZC4).

SUBUNIT: Homotetramer (By similarity)(UniProt: Q8FZC4).

SIMILARITY: Belongs to the alpha-IPM synthetase/homocitrate synthase family. LeuA type 2 subfamily(UniProt: Q8FZC4).

MUTATION: leuA is a B. suis gene identified by signature-tagged mutagenesis. It is attenuated inside THP1 macrophage cell line.
1226 BMEI0455 Brucella 1196166 17986738 BMEI0455 NP_539372.1 GLUTATHIONE S-TRANSFERASE Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: Glutathione S-transferase, C-terminal domain (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1227 pth from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196191 17986763 BMEI0480 NP_539397.1 peptidyl-tRNA hydrolase Virulence factor FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(UniProt: P65864).

CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(UniProt: P65864).

SUBUNIT: Monomer (By similarity)(UniProt: P65864).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: P65864).

SIMILARITY: Belongs to the PTH family(UniProt: P65864).

MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed (Danese et al., 2004).
15385478
1228 lpsB Brucella melitensis bv. 1 str. 16M 1196220 17986792 BMEI0509 NP_539426.1 LIPOPOLYSACCHARIDE CORE BIOSYNTHESIS MANNOSYLTRANSFERASE LPCC Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: Core synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1229 trkH Brucella melitensis bv. 1 str. 16M 1196223 17986795 BMEI0512 NZ_GG703780 NP_539429 thioredoxin reductase Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Thioredoxin reductase (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
14979322
1230 lysR from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196224 17986796 BMEI0513 NP_539430.1 TRANSCRIPTIONAL REGULATORY PROTEIN, LYSR FAMILY Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (Delrue et al., 2004).

FUNCTION: Transcriptional regulator (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1231 aspC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196227 17986799 BMEI0516 NP_539433.1 aspartate aminotransferase Virulence factor MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth (Kim et al., 2003). 12761078
1232 carAB Brucella melitensis bv. 1 str. 16M 1196237 161511156 BMEI0526 NZ_GG703780 NP_539443 carbamoyl phosphate synthase small subunit Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Clut. and pyr. Syntheis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1233 pncA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196256 17986828 BMEI0545 NP_539462.1 INTEGRAL MEMBRANE PROTEIN Virulence factor MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells (Kim et al., 2003). Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages (Kim et al., 2004). The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks (Kim et al., 2004). It indicates that the mutant has reduced virulence in mice. 12761078 15135535
1234 bicA Brucella melitensis bv. 1 str. 16M 1196316 17986888 BMEI0605 AE008917 NP_539522 bicyclomycin resistance protein Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (Delrue et al., 2004).

FUNCTION: Macrolide efflux (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1235 serB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196326 17986898 BMEI0615 NP_539532.1 PHOSPHOSERINE PHOSPHATASE Virulence factor MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis serB gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). 12438693
1236 miaA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196327 17986899 BMEI0616 NP_539533.1 tRNA delta(2)-isopentenylpyrophosphate transferase Virulence factor FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(UniProt: Q8CY40).

CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(UniProt: Q8CY40).

SIMILARITY: Belongs to the IPP transferase family(UniProt: Q8CY40).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
12438693
1237 ilvI Brucella melitensis bv. 1 str. 16M 1196328 17986900 BMEI0617 HD006899 NP_539534 acetolactate synthase 3 catalytic subunit Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Val. Leu., Isoleu. Synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1238 ilvCv from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196335 17986907 BMEI0624 NP_539541.1 ketol-acid reductoisomerase Virulence factor CATALYTIC ACTIVITY: (R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH(UniProt: Q8FZU1).

CATALYTIC ACTIVITY: (2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-hydroxy-2-ethyl-3-oxobutanoate + NADPH(UniProt: Q8FZU1).

PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-isoleucine from 2-oxobutanoate: step 2(UniProt: Q8FZU1).

PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from pyruvate: step 2(UniProt: Q8FZU1).

SIMILARITY: Belongs to the ketol-acid reductoisomerase family(UniProt: Q8FZU1).

MUTATION: ilvC is one of the 37 mutants with virulene defect, screened out from the signature- tagged miniTn5 library (Lestrate et al., 2003).
14638795
1239 aspB from Brucella suis 1330 Brucella suis 1330 1196337 17986909 BMEI0626 NP_539543.1 TRANSCRIPTIONAL REGULATOR, GNTR FAMILY / MULTIPLE SUBSTRATE AMINOTRANSFERASE Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: Aminotransferase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1240 BMEI0671 Brucella 1196382 17986954 BMEI0671 NP_539588.1 INTEGRAL MEMBRANE PROTEIN / HEMOLYSIN Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: Terc dome (efflux) (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1241 cobB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196416 17986988 BMEI0705 NP_539622.1 cobyrinic acid a,c-diamide synthase Virulence factor FUNCTION: Responsible for the amidation of carboxylic groups at position A and C of either cobyrinic acid or hydrogenobrynic acid. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolyzed for each amidation (By similarity)(UniProt: Q8G020).

PATHWAY: Cobalamin biosynthesis(UniProt: Q8G020).

SIMILARITY: Belongs to the cobB/cobQ family. CobB subfamily(UniProt: Q8G020).

MUTATION: 1,152 signature-tagged mutagenesis mutants of Brucella melitensis 16M were screened in a mouse model of infection. 36 of them to be attenuated in vivo. cobB is one of them (Lestrate et al., 2003).
14638795
1242 thrA Brucella melitensis bv. 1 str. 16M 1196436 17987008 BMEI0725 AE008917 NP_539642 homoserine dehydrogenase Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Lys. synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1243 gloA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196441 17987013 BMEI0730 NP_539647.1 LACTOYLGLUTATHIONE LYASE Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
14979322
1244 rpoA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196492 17987064 BMEI0781 NP_539698.1 DNA-directed RNA polymerase subunit alpha Virulence factor FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(UniProt: Q8G094).

CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(UniProt: Q8G094).

SUBUNIT: Homodimer. The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription (By similarity)(UniProt: Q8G094).

DOMAIN: The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity)(UniProt: Q8G094).

SIMILARITY: Belongs to the RNA polymerase alpha chain family(UniProt: Q8G094).

MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress (Lestrate et al., 2003).
14638795
1245 recA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196498 17987070 BMEI0787 NP_539704.1 recombinase A Virulence factor FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(UniProt: P65976).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: P65976).

SIMILARITY: Belongs to the recA family(UniProt: P65976).

MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice (Tatum et al., 1993).

The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persistence phase (Tatum et al., 1993).

8321120
1246 uppS from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196538 17987110 BMEI0827 NP_539744.1 UNDECAPRENYL PYROPHOSPHATE SYNTHETASE Virulence factor FUNCTION: Generates undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate (IPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide (By similarity)(UniProt: Q8G0D9).

CATALYTIC ACTIVITY: Di-trans,poly-cis-decaprenyl diphosphate + isopentenyl diphosphate = diphosphate + di-trans,poly-cis-undecaprenyl diphosphate(UniProt: Q8G0D9).

COFACTOR: Magnesium (By similarity)(UniProt: Q8G0D9).

SUBUNIT: Homodimer (By similarity)(UniProt: Q8G0D9).

SIMILARITY: Belongs to the UPP synthetase family(UniProt: Q8G0D9).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis uppS gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
12438693
1247 ppiD from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196556 17987128 BMEI0845 NP_539762.1 PEPTIDYL-PROLYL CIS-TRANS ISOMERASE D Virulence factor FUNCTIONAL GROUP: Stress proteins/Chaperones (Delrue et al., 2004).

FUNCTION: Rotamase D (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1248 ntrY from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196578 17987150 BMEI0867 NP_539784.1 NITROGEN REGULATION PROTEIN NTRY Virulence factor MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype (Foulongne et al., 2000). 10678941
1249 hfq from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196583 17987155 BMEI0872 NP_539789.1 RNA-binding protein Hfq Virulence factor FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(UniProt: P0A3G8).

SIMILARITY: Belongs to the hfq family(UniProt: P0A3G8).

MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source(Sonnleitner et al., 2003).

hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages (Roop et al., 2003).

In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication (Roop et al., 2003).

A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type (Roop et al., 2003).
14521880 12730323
1250 lon from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196587 17987159 BMEI0876 NP_539793.1 ATP-DEPENDENT PROTEASE LA Virulence factor FUNCTION: Degrades short-lived regulatory and abnormal proteins in presence of ATP. Hydrolyzes two ATPs for each peptide bond cleaved in the protein substrate (By similarity)(UniProt: Q8G0I7).

CATALYTIC ACTIVITY: Hydrolysis of proteins in presence of ATP(UniProt: Q8G0I7).

SUBUNIT: Homotetramer (By similarity)(UniProt: Q8G0I7).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G0I7).

SIMILARITY: Belongs to the peptidase S16 family(UniProt: Q8G0I7).

SIMILARITY: Contains 1 Lon domain(UniProt: Q8G0I7).

MUTATION: In contrast to the parent strain, the Brucella abortus lon mutant, was impaired in its capacity to form isolated colonies on solid medium at 41 degrees C and displayed an increased sensitivity to killing by puromycin and H2O2. Brucella abortus Lon homologue functions as a stress response protease that is required for wild-type virulence during the initial stages of infection in the mouse model, but is not essential for the establishment and maintenance of chronic infection in this host (Robertson et al., 2000).

Both single lon or clpA mutations had comparable effects on growth inhibition, suggesting that the concerned proteases Lon and ClpAP both degrade a number of specific proteins, but are also both involved in general degradation of abnormal proteins. Compared to the single mutants, the double mutant lon clpA was highly sensitive to canavanine. One possible explanation for this observation is that both proteases can substitute for each other to a large extent during bacterial growth. Hence, simultaneous inactivation or decrease in activation of both proteases, either by direct mutation or by elimination of the regulatory component ClpA, strongly increased growth inhibition (Robertson et al., 2000).
10672180
1251 uvrA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196589 17987161 BMEI0878 NP_539795.1 excinuclease ABC subunit A Virulence factor FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(UniProt: Q8G0I9).

SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(UniProt: Q8G0I9).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G0I9).

SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(UniProt: Q8G0I9).

SIMILARITY: Contains 2 ABC transporter domains(UniProt: Q8G0I9).

MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants (Roux et al., 2006).
16816190
1252 gntR5 Brucella 1196592 17987164 BMEI0881 NP_539798.1 TRANSCRIPTIONAL REGULATOR, GNTR FAMILY Virulence factor FUNCTIONAL GROUP: gntR family (Haine et al., 2005).

MUTATION: Attenuated using plasmid-tagged mutagenesis method (Haine et al., 2005).
16113274
1253 caiB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196609 17987181 BMEI0898 NP_539815.1 Predicted acyl-CoA transferase/carnitine dehydratase Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: CAIB/BAIF family (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1254 cysK from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196644 17987216 BMEI0933 NP_539850.1 cysteine synthase A Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Cys. synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1255 glnA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196690 17987262 BMEI0979 NP_539896.1 GLUTAMINE SYNTHETASE Virulence factor MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). 12438693
1256 wbdA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196708 17987280 BMEI0997 NP_539914.1 MANNOSYLTRANSFERASE Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1257 caiB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196730 17987302 BMEI1019 NP_539936.1 molybdenum cofactor biosynthesis protein A Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: CAIB/BAIF family (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1258 dsbA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196751 17987323 BMEI1040 NP_539957.1 ABC TRANSPORTER ATP-BINDING PROTEIN Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Disulfide bond formation protein (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1259 nifS from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196754 17987326 BMEI1043 NP_539960.1 NIFS PROTEIN Virulence factor FUNCTIONAL GROUP: Nitrogen metabolism (Delrue et al., 2004).

FUNCTION: nitrogenase cofactor synthesis protein nifS (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1260 amiC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196767 17987339 BMEI1056 AE008917 NP_539973 N-acetylmuramoyl-L-alanine amidase Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan (Delrue et al., 2004).

FUNCTION: Cell-wall hydrolysis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1261 dsbA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196771 17987343 BMEI1060 NP_539977.1 OUTER MEMBRANE PROTEIN Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Disulfide bond formation protein (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1262 tig from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196780 17987352 BMEI1069 NP_539986.1 trigger factor Virulence factor FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(UniProt: Q8G129).

SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(UniProt: Q8G129).

SIMILARITY: Contains 1 PPIase FKBP-type domain(UniProt: Q8G129).

MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice (Lestrate et al., 2003).
14638795
1263 artI from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196815 17987387 BMEI1104 NP_540021.1 ARGININE/ORNITHINE-BINDING PERIPLASMIC PROTEIN PRECURSOR Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Transport (Delrue et al., 2004).

FUNCTION: Arginine transport system (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
14979322
1264 cbbE Brucella melitensis bv. 1 str. 16M 1196827 17987399 BMEI1116 AE008917 NP_540033 ribulose-phosphate 3-epimerase Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: Ribulose-phosphate 3-epimerase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1265 purL from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196838 17987410 BMEI1127 NP_540044.1 phosphoribosylformylglycinamidine synthase II Virulence factor CATALYTIC ACTIVITY: ATP + N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H(2)O = ADP + phosphate + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine + L-glutamate(UniProt: Q8G183).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 1(UniProt: Q8G183).

PATHWAY: Context: Purine biosynthesis(UniProt: Q8G183).

SUBUNIT: Heterodimer of two subunits, purQ and purL(UniProt: Q8G183).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G183).

SIMILARITY: Belongs to the FGAMS family(UniProt: Q8G183).

MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages (Alcantara et al., 2004). Studies with B melitensis purE and B abortus purL mutants, which are purine auxotrophs, and B suis aroC mutants, which can not synthesize aromatic amino acids, indicate that the brucellae also face signicant nutrient limitation during their prolonged residence in host macrophages (Alcantara et al., 2004).
15271960
1266 glyA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196903 17987475 BMEI1192 NP_540109.1 SERINE HYDROXYMETHYLTRANSFERASE Virulence factor FUNCTION: Interconversion of serine and glycine(UniProt: Q8G1F1).

CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(UniProt: Q8G1F1).

COFACTOR: Pyridoxal phosphate (By similarity)(UniProt: Q8G1F1).

PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(UniProt: Q8G1F1).

SUBUNIT: Homotetramer (By similarity)(UniProt: Q8G1F1).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G1F1).

SIMILARITY: Belongs to the SHMT family(UniProt: Q8G1F1).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
12438693
1267 BMEI1229 Brucella 1196940 17987512 BMEI1229 NP_540146.1 Hypothetical exonuclease Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: Exonuclease X-T domain (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1268 galE from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196948 17987520 BMEI1237 NP_540154.1 UDP-GLUCOSE 4-EPIMERASE Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: UDP-glucose 4-epimerase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1269 purM from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196951 17987523 BMEI1240 NP_540157.1 phosphoribosylaminoimidazole synthetase Virulence factor CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(UniProt: Q8G1K5).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 2(UniProt: Q8G1K5).

PATHWAY: Context: Purine biosynthesis(UniProt: Q8G1K5).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G1K5).

SIMILARITY: Belongs to the AIR synthase family(UniProt: Q8G1K5).

MUTATION: B. abortus purM gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study (Kim et al., 2003).
12761078
1270 purN from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196952 17987524 BMEI1241 NP_540158.1 phosphoribosylglycinamide formyltransferase Virulence factor MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study (Kim et al., 2003). 12761078
1271 omp25 from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196960 17987532 BMEI1249 NP_540166.1 25 KDA OUTER-MEMBRANE IMMUNOGENIC PROTEIN PRECURSOR Virulence factor SUBCELLULAR LOCATION: Outer membrane(UniProt: Q45689).

SIMILARITY: Belongs to the omp25/ropB family(UniProt: Q45689).

MUTATION: In contrast to WT B suis or Deltaomp31 B suis, Deltaomp25 B suis induced TNF-alpha production when phagocytosed by human macrophages. So Omp25 of B suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages (Jubier-Maurin et al., 2001).

To determine the role of Omp25 in virulence, mutants were created with Brucella abortus (BA25), Brucella melitensis (BM25), and Brucella ovis (BO25) which contain disruptions in the omp25 gene (Deltaomp25 mutants). BALBc mice infected with B abortus BA25 or B melitensis BM25 showed a significant decrease in mean CFUspleen at 18 and 4 weeks post-infection, respectively, when compared to the virulent parental strain. Mice infected with B ovis BO25 had significantly lower mean CFUspleen counts from 1 to 8 weeks post-infection, at which point the mutant was cleared from the spleens. Murine vaccination with either BM25 or the current caprine vaccine B melitensis strain Rev.1 resulted in more than a 2log (10) reduction in bacterial load following challenge with virulent B melitensis. Vaccination of mice with the B ovis mutant resulted in clearance of the challenge strain and provided 2.5log (10) greater protection against virulent B ovis than vaccine strain Rev.1. Based on these data, the B melitensis and B ovis Deltaomp25 mutants are interesting vaccine candidates that are currently under study in our laboratory for their safety and efficacy in small ruminants (Jubier-Maurin et al., 2001).

Although they are slightly attenuated, B abortus omp25 and omp22 mutants do not show the high level of attenuation and sensitivity to bactericidal peptides displayed by the bvrS and bvrR mutants (Jubier-Maurin et al., 2001). B abortus mutants carrying Omp25 deletions do not show enrichment of underacylated LPS (Jubier-Maurin et al., 2001).

Brucella spp. omp25 deletion mutants are attenuated in mice, cattle and goats, showing the involvement of Brucella spp. Omp25 in virulence (Jubier-Maurin et al., 2001).
11447156
1272 BMEI1258 Brucella 1196969 17987541 BMEI1258 NP_540175.1 ABC TRANSPORTER ATP-BINDING PROTEIN Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (Delrue et al., 2004).

FUNCTION: ABC transporter (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
14979322
1273 pyrC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1196992 17987564 BMEI1281 NP_540198.1 dihydroorotase Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: dihydroorotase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1274 spotT from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197007 17987579 BMEI1296 NP_540213.1 GUANOSINE-3',5'-BIS(DIPHOSPHATE) 3'-PYROPHOSPHOHYDROLASE Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: ppGpp synthetase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1275 lpsA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197037 17987609 BMEI1326 NP_540243.1 LPSA PROTEIN Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: putative glycosyltranferase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1276 htrA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197041 17987613 BMEI1330 NP_540247.1 PROTEASE DO Virulence factor FUNCTIONAL GROUP: Stress proteins/Chaperones (Kohler et al., 2002).

FUNCTION: Protease (Kohler et al., 2002).

MUTATION: Attenuated in "Goat", Macrophages, but not in Mice (Kohler et al., 2002).
12438693
1277 feuQ from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197047 17987619 BMEI1336 NP_540253.1 SENSOR PROTEIN PHOQ Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Histidine kinase (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1278 feuP from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197048 17987620 BMEI1337 NP_540254.1 TRANSCRIPTIONAL REGULATORY PROTEIN PHOP Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Response regulator (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages (Delrue et al., 2004).
14979322
1279 BMEI1339 Brucella 1197050 17987622 BMEI1339 NP_540256.1 hypothetical protein Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: Brucella/Agrobacterium orphan gene (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1280 BMEI1361 Brucella 1197072 17987644 BMEI1361 NP_540278.1 Hypothetical Cytosolic Protein Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1281 wbpZ from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197104 17987676 BMEI1393 NP_540310.1 MANNOSYLTRANSFERASE C Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages (Delrue et al., 2004).
14979322
1282 pmm from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197107 17987679 BMEI1396 NP_540313.1 PHOSPHOMANNOMUTASE Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1283 wbkA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197115 17987687 BMEI1404 NP_540321.1 MANNOSYLTRANSFERASE Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1284 rfbD from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197124 17987696 BMEI1413 NP_540330.1 GDP-mannose 4,6-dehydratase Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages (Delrue et al., 2004).
14979322
1285 perA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197125 17987697 BMEI1414 NP_540331.1 PEROSAMINE SYNTHETASE Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1286 wbpL from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197137 17987709 BMEI1426 NP_540343.1 PUTATIVE UNDECAPRENYL-PHOSPHATE ALPHA-N-ACETYLGLUCOSAMINYLTRANSFERASE Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages (Delrue et al., 2004).
14979322
1287 dsbA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197151 17987723 BMEI1440 NP_540357.1 THIOL:DISULFIDE INTERCHANGE PROTEIN DSBA Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Disulfide bond formation protein (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1288 BMEI1443 Brucella 1197154 17987726 BMEI1443 NP_540360.1 2-HALOALKANOIC ACID DEHALOGENASE I Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: haloacid dehalogenase-like hydrolase domain (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1289 BMEI1448 Brucella 1197159 17987731 BMEI1448 NP_540365.1 C-DI-GMP PHOSPHODIESTERASE A-RELATED PROTEIN Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: EAL domain (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1290 thrC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197161 17987733 BMEI1450 NP_540367.1 threonine synthase Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Thre. Synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1291 tldD from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197179 17987751 BMEI1468 NP_540385.1 TLDD PROTEIN Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation (Delrue et al., 2004).

FUNCTION: Putative modulator of DNA gyrase (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1292 purF from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197199 17987771 BMEI1488 NP_540405.1 amidophosphoribosyltransferase Virulence factor MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth (Kim et al., 2003). 12761078
1293 dxps Brucella melitensis bv. 1 str. 16M 1197209 17987781 BMEI1498 NZ_GG703778 NP_540415 1-deoxy-D-xylulose-5-phosphate synthase Virulence factor FUNCTIONAL GROUP: Vitamines cofactors (Delrue et al., 2004).

FUNCTION: Thiamine synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
14979322
1294 aroC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197217 17987789 BMEI1506 NP_540423.1 chorismate synthase Virulence factor CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(UniProt: P63608).

COFACTOR: Reduced flavin (By similarity)(UniProt: P63608).

PATHWAY: Metabolic intermediate biosynthesis; chorismate biosynthesis; chorismate from D-erythrose 4-phosphate and PEP: step 7 [final step](UniProt: P63608).

PATHWAY: Context: Aromatic amino acids biosynthesis(UniProt: P63608).

SUBUNIT: Homotetramer (By similarity)(UniProt: P63608).

SIMILARITY: Belongs to the chorismate synthase family(UniProt: P63608).

MUTATION: The cloned aroC gene complements Escherichia coli and Salmonella enterica serovar Typhimurium aroC mutants. A B suis aroC mutant was found to be unable to grow in a defined medium without aromatic compounds. The mutant was highly attenuated in it issue culture (THP1 macrophages and HeLa cells) and murine virulence models (Foulongne et al., 2001).
11119550
1295 purD from Brucella melitensis bv. 1 str. 16M B rucella melitensis bv. 1 str. 16M 1197230 17987802 BMEI1519 NP_540436.1 phosphoribosylamine--glycine ligase Virulence factor CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(UniProt: Q8G2B1).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; N(1)-(5-phospho-D-ribosyl)glycinamide from 5-phospho-alpha-D-ribose 1-diphosphate: step 2(UniProt: Q8G2B1).

PATHWAY: Context: Purine biosynthesis(UniProt: Q8G2B1).

SIMILARITY: Belongs to the GARS family(UniProt: Q8G2B1).

SIMILARITY: Contains 1 ATP-grasp domain(UniProt: Q8G2B1).

MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages (Alcantara et al., 2004).

Like the purE mutant, a purD::Tn10 mutant has reduced survival in murine macrophages and reduced virulence in mice (Alcantara et al., 2004).
15271960
1296 BMEI1531 Brucella 1197242 17987814 BMEI1531 NP_540448.1 TETRATRICOPEPTIDE REPEAT FAMILY PROTEIN Virulence factor FUNCTIONAL GROUP: Other genes (Delrue et al., 2004).

FUNCTION: protein-protein interaction (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1297 bacA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197264 17987836 BMEI1553 NP_540470.1 transport protein Virulence factor MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain (LeVier et al., 2000). R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis (LeVier et al., 2000). The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria(Ferguson et al., 2002). 10741969 12270820
1298 lysR18 Brucella 1197284 17987856 BMEI1573 NP_540490.1 TRANSCRIPTIONAL REGULATORY PROTEIN, LYSR FAMILY Virulence factor FUNCTIONAL GROUP: lysR family (Haine et al., 2005).

MUTATION: Attenuated using plasmid-tagged mutagenesis method (Haine et al., 2005).
16113274
1299 vsrB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197317 17987889 BMEI1606 NP_540523.1 SENSORY TRANSDUCTION HISTIDINE KINASE Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Histidine kinase (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1300 pyrD from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197322 17987894 BMEI1611 NP_540528.1 dihydroorotate dehydrogenase 2 Virulence factor MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth (Kim et al., 2003). 12761078
1301 pgi from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197347 17987919 BMEI1636 NP_540553.1 glucose-6-phosphate isomerase Virulence factor CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(UniProt: Q8G2N3).

PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 2(UniProt: Q8G2N3).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G2N3).

SIMILARITY: Belongs to the GPI family(UniProt: Q8G2N3).

MUTATION: B. suis pgi is a gene identified by signature-tagged mutagenesis. The mutant is attenuated inside THP1 macrophages. The mutation of the pgi gene could also affect the biosynthesis of the bacterial peptidoglycan (Foulongne et al., 2000).
10678941
1302 BMEI1658 Brucella 1197369 17987941 BMEI1658 NP_540575.1 hypothetical protein Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: Brucella orphan gene (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1303 hisD from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197379 17987951 BMEI1668 NP_540585.1 histidinol dehydrogenase Virulence factor FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(UniProt: Q8G2R2).

CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(UniProt: Q8G2R2).

COFACTOR: Binds 1 zinc ion per subunit (By similarity)(UniProt: Q8G2R2).

PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 9 [final step](UniProt: Q8G2R2).

SIMILARITY: Belongs to the histidinol dehydrogenase family(UniProt: Q8G2R2).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis hisD gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
12438693
1304 malK from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197424 17987996 BMEI1713 NP_540630.1 MALTOSE/MALTODEXTRIN TRANSPORT ATP-BINDING PROTEIN MALK Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Transport (Delrue et al., 2004).

FUNCTION: Maltose transport (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, but not in HeLa (Delrue et al., 2004).
14979322
1305 exsA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197453 17988025 BMEI1742 NP_540659.1 ABC TRANSPORTER ATP-BINDING PROTEIN Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Transport (Delrue et al., 2004).

FUNCTION: ABC transporter (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1306 metH from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197470 17988042 BMEI1759 NP_540676.1 B12-dependent methionine synthase Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Met. synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1307 cysI from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197477 17988049 BMEI1766 NP_540683.1 SULFITE REDUCTASE (FERREDOXIN) Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Sulfite reductate (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, but not in HeLa (Delrue et al., 2004).
14979322
1308 glnL Brucella melitensis bv. 1 str. 16M 1197497 17988069 BMEI1786 NZ_GG703778 NP_540703 nitrogen regulatory IIA protein Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Nitrogen regulatory IIA (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1309 glnD from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197515 17988087 BMEI1804 NP_540721.1 PII uridylyl-transferase Virulence factor FUNCTION: Modifies, by uridylylation or deuridylylation the PII (glnB) regulatory protein (By similarity)(UniProt: Q8G312).

CATALYTIC ACTIVITY: UTP + [protein-PII] = diphosphate + uridylyl-[protein-PII](UniProt: Q8G312).

SIMILARITY: Belongs to the glnD family(UniProt: Q8G312).

MUTATION: glnD encodes for a uridylyl transferase which is the primary sensor of nitrogen. The glnD mutant via signature-tagged transposon mutagenesis is attenuated in THP1 macrophages and HeLa cells. It supports the hypothesis that the concentration of glutamine in host cells is critical for the intracellular survival of Brucella (Foulongne et al., 2000).
10678941
1310 BMEI1809 Brucella 1197520 17988092 BMEI1809 NP_540726.1 PROTEIN YBIS PRECURSOR Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: ERFK/YBIS/YCFS/YNHG family (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1311 ndvB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197548 17988120 BMEI1837 NP_540754.1 CELLOBIOSE-PHOSPHORYLASE Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: Synthesis of cyclic ( (Delrue et al., 2004).

MUTATION: Attenuated in Mice, HeLa (Delrue et al., 2004).
14979322
1312 BMEI1844 Brucella 1197555 17988127 BMEI1844 NP_540761.1 hypothetical protein Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: Domain of Unkown Function (DUF930) (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1313 ilvD from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197559 17988131 BMEI1848 NP_540765.1 dihydroxy-acid dehydratase Virulence factor CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(UniProt: Q8G353).

COFACTOR: Binds 1 4Fe-4S cluster (Potential)(UniProt: Q8G353).

PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-isoleucine from 2-oxobutanoate: step 3(UniProt: Q8G353).

PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from pyruvate: step 3(UniProt: Q8G353).

SIMILARITY: Belongs to the ilvD/edd family(UniProt: Q8G353).

MUTATION: Of those B abortus mutants with mini-Tn5 insertions in genes predicted to be involved in amino acid biosynthesis and transport, only the ilvD mutant, displayed attenuation in both macrophages and mice. The othre two amino acid biosynthesis mutants [trpB::miniTn5 and pheA::miniTn5] displayed wild-type virulence in mice but attenuated inside macrophages. The studies with B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not (Alcantara et al., 2004).
15271960
1314 cysY Brucella melitensis bv. 1 str. 16M 1197560 17988132 BMEI1849 NZ_GG703778 NP_540766 thiol:disulfide interchange protein CYCY precursor Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Disulfide oxidoreducate (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1315 BMEI1859 Brucella 1197570 17988142 BMEI1859 NP_540776.1 INTEGRAL MEMBRANE PROTEIN Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: Uncharacterised protein family 0005 (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1316 BMEI1879 Brucella 1197590 17988162 BMEI1879 NP_540796.1 Hypothetical Cytosolic Protein Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: Brucella/Mesorhizobium orphan gene (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1317 pgm from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197597 17988169 BMEI1886 NP_540803.1 phosphoglucomutase Virulence factor MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells (Ugalde et al., 2000).

B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro (Ko and Splitter, 2003).
10992476 12525425
1318 BMEI1902 Brucella 1197613 17988185 BMEI1902 NP_540819.1 Molybdopterin biosynthesis enzyme Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: Brucella/Mesorhizobium orphan gene (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1319 lysR13 Brucella 1197624 17988196 BMEI1913 NP_540830.1 TRANSCRIPTIONAL REGULATORY PROTEIN, LYSR FAMILY Virulence factor FUNCTIONAL GROUP: lysR family (Haine et al., 2005).

MUTATION: Attenuated using plasmid-tagged mutagenesis method (Haine et al., 2005).
16113274
1320 rpsA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197626 17988198 BMEI1915 NP_540832.1 30S ribosomal protein S1 Virulence factor MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis (Foulongne et al., 2000). 10678941
1321 mutM from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197657 17988229 BMEI1946 NP_540863.1 formamidopyrimidine-DNA glycosylase Virulence factor FUNCTION: Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates (By similarity)(UniProt: Q8FXR6).

CATALYTIC ACTIVITY: Hydrolysis of DNA containing ring-opened N(7)-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine(UniProt: Q8FXR6).

CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate(UniProt: Q8FXR6).

COFACTOR: Binds 1 zinc ion per subunit (By similarity)(UniProt: Q8FXR6).

SUBUNIT: Monomer (By similarity)(UniProt: Q8FXR6).

SIMILARITY: Belongs to the FPG family(UniProt: Q8FXR6).

SIMILARITY: Contains 1 FPG-type zinc finger(UniProt: Q8FXR6).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
14979322
1322 dnaK from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197713 17988285 BMEI2002 NP_540919.1 molecular chaperone DnaK Virulence factor FUNCTION: Acts as a chaperone (By similarity)(UniProt: Q8FXX2).

INDUCTION: By stress conditions e.g. heat shock (By similarity)(UniProt: Q8FXX2).

SIMILARITY: Belongs to the heat shock protein 70 family(UniProt: Q8FXX2).

MUTATION: The heat shock protein DnaK is essential for intramacrophagic replication of Brucella suis. The replacement of the stress-inducible, native dnaK promoter of B suis by the promoter of the constitutively expressed bla gene resulted in temperature-independent synthesis of DnaK. In contrast to a dnaK null mutant, this strain grew at 37 degrees C, with a thermal cutoff at 39 degrees C However, the constitutive dnaK mutant, which showed high sensitivity to H(2)O(2)-mediated stress , failed to multiply in murine macrophage-like cells and was rapidly eliminated in a mouse model of infection, adding strong arguments that stress-mediated and heat shock promoter-dependent induction of dnaK is a crucial event in the intracellular replication of B suis (Köhler et al., 2002).

Mutation studies indicated that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. Viability of the dnaK null mutant was also greatly affected at low pH. In infection experiments performed with both mutants at the reduced temperature of 30 degrees C, the dnaK mutant of B suis survived but failed to multiply within U937 cells, whereas the wild-type strain and the dnaJ mutant multiplied normally. Complementation of the dnaK mutant with the cloned dnaK gene restored growth at 37 degrees C, increased resistance to acid pH, and increased intracellular multiplication (Köhler et al., 2002).
11854256
1323 bvrS from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197746 17988318 BMEI2035 NP_540952.1 SENSOR PROTEIN CHVG Virulence factor MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly (Manterola et al., 2005).

Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism (López-Goñi et al., 2002).

In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments (Pizarro-Cerdá et al., 1998).

B abortus bvrS bvrR mutants display reduced invasiveness and virulence (Briones et al., 2001).

Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact (Gorvel and Moreno, 2002).

Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments (Guzman-Verri et al., 2002).

BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly (Guzman-Verri et al., 2002).
16077108 12414153 9826346 11401996 12414149 12218183
1324 bvrR from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197747 17988319 BMEI2036 NP_540953.1 TRANSCRIPTIONAL REGULATORY PROTEIN CHVI Virulence factor MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly (Manterola et al., 2005).

Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism (López-Goñi et al., 2002).

In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments (Pizarro-Cerdá et al., 1998).

B abortus bvrS bvrR mutants display reduced invasiveness and virulence (Briones et al., 2001).

Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact (Gorvel and Moreno, 2002).

Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments (Guzman-Verri et al., 2002).

BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly (Guzman-Verri et al., 2002).
16077108 12414153 9826346 11401996 12414149 12218183
1325 hisF from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197752 17988324 BMEI2041 NP_540958.1 imidazole glycerol phosphate synthase subunit HisF Virulence factor FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(UniProt: Q8FY07).

CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(UniProt: Q8FY07).

PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 5(UniProt: Q8FY07).

SUBUNIT: Heterodimer of hisH and hisF (By similarity)(UniProt: Q8FY07).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8FY07).

SIMILARITY: Belongs to the hisA/hisF family(UniProt: Q8FY07).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis hisF gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
12438693
1326 omp10 from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197788 17988361 BMEII0017 NP_540994.1 OUTER MEMBRANE LIPOPROTEIN Virulence factor SUBCELLULAR LOCATION: Outer membrane; lipid-anchor(UniProt: P0A3N9).

MISCELLANEOUS: Elicits an immune response in B.melitensis-infected sheep but not in B.abortus-infected cattle(UniProt: P0A3N9).

SIMILARITY: Belongs to the rhizobiaceae omp10 lipoprotein family(UniProt: P0A3N9).

MUTATION: Omp10 is an immunoreactive outer membrane lipoprotein. The omp10 mutant was dramatically attenuated for survival in mice and was defective for growth in minimal medium but was not impaired in intracellular growth in vitro, nor does it display clear modification of the outer membrane properties (Tibor et al., 2002).
12228280
1327 hemH from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197789 17988362 BMEII0018 NP_540995.1 ferrochelatase Virulence factor FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(UniProt: P0A3D7).

CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(UniProt: P0A3D7).

PATHWAY: Protoheme biosynthesis; last step(UniProt: P0A3D7).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: P0A3D7).

SIMILARITY: Belongs to the ferrochelatase family(UniProt: P0A3D7).

MUTATION: A hemH knockout B. abortus mutant displayed auxotrophy for hemin, defective intracellular survival inside J774 and HeLa cells, and lack of virulence in BALBc mice. This phenotype was overcome by complementing the mutant strain with a plasmid harboring wild-type hemH. These data demonstrate that B abortus synthesizes its own heme and also has the ability to use an external source of heme (Almirón et al., 2001).
11553564
1328 virb1 Brucella melitensis bv. 1 str. 16M 1197796 17988369 BMEII0025 AE008918 NP_541002 attachment mediating protein VIRB1-like protein Virulence factor MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB1 mutant persisted at wild-type levels, showing that the function of VirB1 is dispensable in the mouse model of persistent infection (den et al., 2004).

A B abortus polar virB1 mutant failed to replicate in HeLa cells, indicating that the virB operon plays a critical role in intracellular multiplication (Sieira et al., 2000).

Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis (Sun et al., 2005).

An infection assay with signature-tagged Brucella abortus mutants demonstrated that mutagenesis of the virB1 gene causes attenuation of virulence (Höppner et al., 2005).
15322008 10940027 16113325 16272371
1329 virB2 from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197797 17988370 BMEII0026 NP_541003.1 VirB2 Virulence factor MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection (den et al., 2004).

Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis (Sun et al., 2005).
15322008 16113325
1330 virB3 from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197798 17988371 BMEII0027 NP_541004.1 VirB3 Virulence factor MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells (Kim et al., 2003). 12761078
1331 virb4 from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197799 17988372 BMEII0028 NP_541005.1 ATPASE VIRB4 HOMOLOG Virulence factor MUTATION: A mutant strain of B abortus that contains an in-frame deletion in virB4 is unable to replicate in macrophages and survives in mice (Watarai et al., 2002). ntracellular replication was inhibited in wild-type B abortus after introducing a plasmid expressing a mutant VirB4 altered in the NTP -binding region. VirB4 containing the intact NTP -binding region is essential for evasion of fusion with lysosomes (11988518).

The ruffling associated with internalization of the virB4 mutant results in a more rapid uptake than for the wild-type strain. The virB4 mutant shows primarily small regions of phalloidin staining at the sites of binding. Macrophages incubated simultaneously with B abortus and the fluid-phase marker tetramethyl rhodamine isothiocyanate (TRITC)-dextran accumulate the marker in large vacuoles containing the wild-type strain, but little or no marker accumulates in phagosomes containing the virB4 mutant. Similarly, phase-contrast micrographs have shown the wild-type strain in large phase-transparent compartments, but the virB4 mutant is in much smaller compartments (14738898).

Intracellular growth-defective virB4 mutant and attenuated vaccine strain S19 did not induce abortion (Kim et al., 2005).

The B abortus virB4 mutant was completely cleared from the spleens of mice after 4 weeks, while the pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from spleens after 10 weeks. Splenomegaly was not observed at all in mice infected with virB4 mutant (Kim et al., 2004).
11988518 15869716 15135535
1332 virB5 from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197800 17988373 BMEII0029 NP_541006.1 VirB5 Virulence factor MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon (Rouot et al., 2003).

Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion (Porte et al., 2003).

Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels (Sun et al., 2005).

Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages (O'Callaghan et al., 1999).
12595417 12595466 16113325 10510235
1333 virb6 from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197801 17988374 BMEII0030 NP_541007.1 CHANNEL PROTEIN VIRB6 HOMOLOG Virulence factor MUTATION: B. abortus virB6 is essential for intracellular growth within HeLa cells as shown from a mutagenesis study.
1334 virB8 from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197803 17988376 BMEII0032 NP_541009.1 VirB8 Virulence factor MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis (Foulongne et al., 2000). Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection (Gorvel and Moreno, 2002). 10678941 12414149
1335 virb9 from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197804 17988377 BMEII0033 NP_541010.1 CHANNEL PROTEIN VIRB9 HOMOLOG Virulence factor MUTATION: Uptake in the presence or absence of Ca2 and Mg2 did not influence the subsequent intracellular survival of wild-type Brucella, whereas the decrease in the number of surviving virB9 mutant cells was delayed in the absence of Ca2 and Mg2. Possibly two types of adhesion molecules promoted uptake of Brucella, one being Ca2 and Mg2 dependent and the other not, and that both types participate in the uptake of wild-type bacteria but only the latter type participates in the uptake of the virB9 mutant (Rittig et al., 2001).

Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages (O'Callaghan et al., 1999).

The intracellular fate of three virB mutants (virB2, virB4 and virB9) in HeLa cells by immunofluorescence was examined. The three VirB proteins are not necessary for penetration and the inhibition of phago-lysosomal fusion within non-professional phagocytes. Rather, the virB mutants are unable to reach the replicative niche and reside in a membrane -bound vacuole expressing the late endosomal marker, LAMP1, and the sec61beta protein from the ER membrane, proteins that are present in autophagic vesicles originating from the ER (Delrue et al., 2001).

Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1 -positive early compartments and then localize in LAMP1-positive compartments at early times of infection (Gorvel and Moreno, 2002).
11349069 10510235 11437834 12414149
1336 virb10 Brucella melitensis bv. 1 str. 16M 1197805 17988378 BMEII0034 AE008918 NP_541011 channel protein VIRB10-like protein Virulence factor MUTATION: Mutants with polar and nonpolar mutations introduced in irB10 showed different behaviors in mice and in the HeLa cell infection assay, suggesting that virB10 per se is necessary for the correct function of this type IV secretion apparatus (Sieira et al., 2000).

A B. abortus virB10 mutant showed a decrease of intracellular live bacteria comparable to that of the wild-type strain until 4 h after infection, indicating that a functional VirB system is not required for the short-term survival of Brucella inside macrophages. At later time points, the number of live virB10 mutants progressively decreased. Hence, the Brucella virB10 strain did not replicate, but rather was killed. Although the virB10 mutants are capable of short-term survival, they can not evade long-term degradation through fusion with lysosomes (Celli et al., 2003).

B abortus virB1 and virB10 mutants are unable to persist in mouse spleens after i.p. inoculation, suggest that attenuation in the animal model is due to an inability of these strains to grow intracellularly (Hong et al., 2000).

A B abortus virB10 mutant lost the ability to multiply in HeLa cells and was not recovered from the spleens of infected BALBc mice (Briones et al., 2001).

The non polar virB10 mutant was able to block the acquisition of cathepsin D, but was not able to translocate to the replication compartment (Boschiroli et al., 2002).

The virB10 non-polar mutants were capable of avoiding interactions with the endocytic pathway but , diverging to wild-type Brucella, were unable to reach the endoplasmic reticulum to establish their intracellular replication niche and seemed to be recycled to the cell surface (Comerci et al., 2001).
10940027 12925673 10858227 11401996 12414154 11260139
1337 virb11 from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197806 17988379 BMEII0035 NP_541012.1 ATPASE VIRB11 HOMOLOG Virulence factor MUTATION: The virB11 mutation experiment confirms that a complete VirB apparatus is required for their secretion (Marchesini et al., 2004). 15312849
1338 gltD Brucella melitensis bv. 1 str. 16M 1197810 161511181 BMEII0039 AE008918 NP_541016 glutamate synthase subunit beta Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Glut. sunthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1339 gltD from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197811 17988384 BMEII0040 NP_541017.1 GLUTAMATE SYNTHASE [NADPH] LARGE CHAIN Virulence factor MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus (Hong et al., 2000). 10858227
1340 nodV from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197823 17988396 BMEII0052 NP_541029.1 SENSORY TRANSDUCTION HISTIDINE KINASE Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Histidine kinase (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1341 mgtB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197827 17988400 BMEII0056 NP_541033.1 MG(2+) TRANSPORT ATPASE, P-TYPE Virulence factor FUNCTIONAL GROUP: Metal acquisition (Delrue et al., 2004).

FUNCTION: Mg2+ uptake (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1342 dhbC Brucella melitensis bv. 1 str. 16M 1197848 17988421 BMEII0077 AE008918 NP_541054 isochorismate synthase Virulence factor FUNCTIONAL GROUP: Metal acquisition (Delrue et al., 2004).

FUNCTION: Sideophore sysnhesis, Fe3+ uptake (Delrue et al., 2004).

MUTATION: Attenuated in Pregant goat, but not in Mice, IFN-/-Mice, Macrophages, Trophoblastes (Delrue et al., 2004).
14979322
1343 rbsK from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197860 17988433 BMEII0089 NP_541066.1 RIBOKINASE Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: Ribokinase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1344 gntR10 Brucella melitensis bv. 1 str. 16M 1197887 17988460 BMEII0116 GG703779 NP_541093 GntR family transcriptional regulator Virulence factor FUNCTIONAL GROUP: gntR family (Haine et al., 2005).

MUTATION: Attenuated using plasmid-tagged mutagenesis method (Haine et al., 2005).
16113274
1345 BMEII0128 Brucella 1197899 17988472 BMEII0128 NP_541105.1 hypothetical protein Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: Uncharacterised protein family (DUF0261) (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1346 pheB Brucella melitensis bv. 1 str. 16M 1197907 17988480 BMEII0136 AE008918 NP_541113 homoprotocatechuate 2,3-dioxygenase Virulence factor FUNCTIONAL GROUP: Other genes (Delrue et al., 2004).

FUNCTION: Dioxygenase (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1347 fliC Brucella melitensis bv. 1 str. 16M 1197921 17988494 BMEII0150 AE008918 NP_541127 flagellin Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (Delrue et al., 2004).

FUNCTION: Flagellin (Delrue et al., 2004).

MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (Delrue et al., 2004).
14979322
1348 fliF from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197922 17988495 BMEII0151 NP_541128.1 FLAGELLAR M-RING PROTEIN FLIF Virulence factor FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(UniProt: Q8FUS3).

SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(UniProt: Q8FUS3).

SUBCELLULAR LOCATION: Inner membrane; multi-pass membrane protein (By similarity)(UniProt: Q8FUS3).

SIMILARITY: Belongs to the fliF family(UniProt: Q8FUS3).

MUTATION: fliF is a gene potentially coding for the MS ring, a basal component of the flagellar system. Its mutant through signature- tagged mutagenesis is attenuated in vivo. It implicate a role for flagella in virulenc (Lestrate et al., 2003).
14638795
1349 motB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197925 17988498 BMEII0154 NP_541131.1 flagellar motor protein MotB Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (Delrue et al., 2004).

FUNCTION: Flagellar motor (Delrue et al., 2004).

MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (Delrue et al., 2004).
14979322
1350 ftcR Brucella melitensis bv. 1 str. 16M 1197929 17988502 BMEII0158 NZ_GG703779 NP_541135 two component response regulator Virulence factor MUTATION: FtcR is required in B melitensis 16M for the transcription of the fliF gene during vegetative and intracellular growth, and for the production of the two structural flagellar components FlgE and FliC during vegetative growth. A ftcR mutant has the same virulence phenotype as previously found with structural flagellar mutants. In HeLa cells and bovine macrophages, no attenuation of the ftcR mutant was observed compared to the WT parental strain. In BALB/c mice, the ftcR mutant was not attenuated after 1 week of infection but was attenuated after 4 weeks of infection. FtcR acts as a flagellar master regulator in B melitensis and perhaps in other related alpha-proteobacteria (Léonard et al., 2007). 17056750
1351 flgE from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197930 17988503 BMEII0159 NP_541136.1 flagellar hook protein FlgE Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (Delrue et al., 2004).

FUNCTION: Hook (Delrue et al., 2004).

SIMILARITY: Belongs to the flagella basal body rod proteins family(UniProt: Q8FUS9).

MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (Delrue et al., 2004).
14979322
1352 flghA Brucella melitensis bv. 1 str. 16M 1197937 17988510 BMEII0166 AE008918 NP_541143 flagellar biosynthetic protein FlhA Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (Delrue et al., 2004).

FUNCTION: Export apparatus (Delrue et al., 2004).

MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (Delrue et al., 2004).
14979322
1353 znuC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197948 17988521 BMEII0177 NP_541154.1 HIGH-AFFINITY ZINC UPTAKE SYSTEM ATP-BINDING PROTEIN ZNUC Virulence factor FUNCTIONAL GROUP: Metal acquisition (Delrue et al., 2004).

FUNCTION: Zn2+ uptake (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1354 znuA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1197949 17988522 BMEII0178 AE008918 NP_541155 high-affinity zinc uptake system protein ZNUA Virulence factor MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells (Kim et al., 2003). High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth (Kim et al., 2004). 12761078 15472468
1355 BMEII0274 Brucella 1198045 17988618 BMEII0274 NP_541251.1 GTPase EngB Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: GTPase of unknown function domain, FeoB domain (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1356 dbsA Brucella melitensis bv. 1 str. 16M 1198072 17988645 BMEII0300 AE008918 NP_541278 ribose ABC transporter ATP-binding protein Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Transport (Delrue et al., 2004).

FUNCTION: Ribose transport (Delrue et al., 2004).

MUTATION: Attenuated in HeLa (Delrue et al., 2004).
14979322
1357 cobW from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198080 17988653 BMEII0308 NP_541286.1 LOW AFFINITY ZINC TRANSPORT MEMBRANE PROTEIN Virulence factor MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis cobW gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). 12438693
1358 BMEII0318 Brucella 1198090 17988663 BMEII0318 NP_541296.1 6-AMINOHEXANOATE-DIMER HYDROLASE Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1359 BMEII0336 Brucella 1198108 17988681 BMEII0336 NP_541314.1 ABC TRANSPORTER PERMEASE PROTEIN Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (Delrue et al., 2004).

FUNCTION: ABC transporter (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1360 dacF from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198122 17988695 BMEII0350 NP_541328.1 D-aminopeptidase Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan (Delrue et al., 2004).

FUNCTION: Peptidoglycan synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1361 araG from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198133 17988706 BMEII0361 NP_541339.1 SUGAR TRANSPORT ATP-BINDING PROTEIN Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Transport (Delrue et al., 2004).

FUNCTION: L-arabinose transport (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages (Delrue et al., 2004).
14979322
1362 fdhA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198150 17988723 BMEII0378 NP_541356.1 FORMATE DEHYDROGENASE ALPHA CHAIN Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Formate dehydrogenase (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1363 lysR12 Brucella 1198162 17988735 BMEII0390 NP_541368.1 TRANSCRIPTIONAL REGULATORY PROTEIN, LYSR FAMILY Virulence factor FUNCTIONAL GROUP: lysR family (Haine et al., 2005).

MUTATION: Attenuated using plasmid-tagged mutagenesis method (Haine et al., 2005).
16113274
1364 eryC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198200 17988773 BMEII0428 NP_541406.1 D-erythrulose 4-phosphate dehydrogenase Virulence factor MUTATION: The eryC gene encodes for enzyme Derythrulose-1-phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 (Sangari et al., 2000).

Allelic exchange mutants in eryC of Brucella suis were erythritol sensitive in vitro with a MIC of 1 to 5 mM of erythritol. Their multiplication in macrophage-like cells was 50 to 90- fold reduced , but complementation of the mutant restored wild-type levels of intracellular multiplication and the capacity to use erythritol as a sole carbon source. In vivo, the eryC mutant colonized the spleens of infected BALBc mice to a significantly lower extent than the wild type and the complemented strain. Interestingly, eryC mutants that were in addition spontaneously erythritol tolerant nevertheless exhibited wild-type-like intramacrophagic and intramurine replication. In conclusion, erythritol was not an essential carbon source for the pathogen in the macrophage host cell but that the inactivation of the eryC gene significantly reduced the intramacrophagic and intramurine fitness of B suis (Burkhardt et al., 2005).
10708387 16177356
1365 eryB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198201 17988774 BMEII0429 NP_541407.1 glycerol-3-phosphate dehydrogenase Virulence factor MUTATION: EryB is an erythritol phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 (Sangari et al., 2000).

The B. suis eryB mutant by Tn5 transposon mutagenesis was attenuated in the human macrophage -like THP-1 cells. This mutant is sensitive to erythritol and mimics the erythritol sensitive response of the B19 strain (Burkhardt et al., 2005).
10708387 16177356
1366 gntR1 Brucella melitensis bv. 1 str. 16M 1198247 17988820 BMEII0475 AE008918 NP_541453 GntR family transcriptional regulator Virulence factor FUNCTIONAL GROUP: gntR family (Haine et al., 2005).

MUTATION: Attenuated using plasmid-tagged mutagenesis method (Haine et al., 2005).
16113274
1367 galcD from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198257 17988830 BMEII0485 NP_541463.1 D-GALACTARATE DEHYDRATASE Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: D-galactarate dehydratase (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1368 nikA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198259 17988832 BMEII0487 NP_541465.1 NICKEL-BINDING PERIPLASMIC PROTEIN PRECURSOR Virulence factor FUNCTIONAL GROUP: Metal acquisition (Delrue et al., 2004).

FUNCTION: Ni2+ uptake (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages, Mice (Delrue et al., 2004).
14979322
1369 zwf from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198285 17988858 BMEII0513 NP_541491.1 glucose-6-phosphate 1-dehydrogenase Virulence factor MUTATION: Brucella abortus zwf mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells and macrophages (Kim et al., 2003). 12761078
1370 xseA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198299 17988872 BMEII0527 NP_541505.1 exodeoxyribonuclease VII large subunit Virulence factor FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(UniProt: Q8FVR1).

CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(UniProt: Q8FVR1).

SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(UniProt: Q8FVR1).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8FVR1).

SIMILARITY: Belongs to the xseA family(UniProt: Q8FVR1).

MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice (Lestrate et al., 2003).
14638795
1371 mocC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198342 17988915 BMEII0570 NP_541548.1 IOLE PROTEIN Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: Rhizopine/inositol catabolism (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction, Mice, but not in Macrophages, HeLa (Delrue et al., 2004).
14979322
1372 RpiR from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198345 17988918 BMEII0573 NP_541551.1 TRANSCRIPTIONAL REGULATOR, RPIR FAMILY Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Transcriptional regulator (Delrue et al., 2004).

MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (Delrue et al., 2004).
14979322
1373 sodC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198353 17988926 BMEII0581 NP_541559.1 SUPEROXIDE DISMUTASE (CU-ZN) Virulence factor FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(UniProt: P66827).

CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(UniProt: P66827).

COFACTOR: Binds 1 copper ion per subunit (By similarity)(UniProt: P66827).

COFACTOR: Binds 1 zinc ion per subunit (By similarity)(UniProt: P66827).

SUBUNIT: Homodimer (By similarity)(UniProt: P66827).

SUBCELLULAR LOCATION: Periplasmic (By similarity)(UniProt: P66827).

SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(UniProt: P66827).

IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-γ, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development (Vemulapalli et al., 2000; Vemulapalli et al., 2000; Vemulapalli et al., 2000).

MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages (Vemulapalli et al., 2000).
10816475
1374 fbpA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198356 17988929 BMEII0584 NP_541562.1 IRON(III)-BINDING PERIPLASMIC PROTEIN PRECURSOR Virulence factor FUNCTIONAL GROUP: Metal acquisition (Delrue et al., 2004).

FUNCTION: Fe3+ binding (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
14979322
1375 ugpA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198363 17988936 BMEII0591 NP_541569.1 SUGAR TRANSPORT SYSTEM PERMEASE PROTEIN Virulence factor MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice (Lestrate et al., 2003). 14638795
1376 ugpA from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198396 17988969 BMEII0624 NP_541602.1 SN-GLYCEROL-3-PHOSPHATE TRANSPORT SYSTEM PERMEASE PROTEIN UGPA Virulence factor MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice (Lestrate et al., 2003). 14638795
1377 BMEII0626 Brucella 1198398 17988971 BMEII0626 NP_541604.1 MEMBRANE DIPEPTIDASE Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: Dipeptidase domain (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1378 divK from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198431 17989004 BMEII0659 NP_541637.1 TWO COMPONENT RESPONSE REGULATOR Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Response regulator (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1379 pyrC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198441 17989014 BMEII0669 NP_541647.1 dihydroorotase Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: dihydroorotase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1380 pyrB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198442 17989015 BMEII0670 NP_541648.1 aspartate carbamoyltransferase catalytic subunit Virulence factor CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(UniProt: P65612).

PATHWAY: Nucleotide biosynthesis; UMP biosynthesis; UMP from HCO(3)(-): step 2(UniProt: P65612).

PATHWAY: Context: Pyrimidine biosynthesis(UniProt: P65612).

SIMILARITY: Belongs to the ATCase/OTCase family(UniProt: P65612).

MUTATION: B. abortus pyrB (pyrimidines) gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study (Kim et al., 2003).
12761078
1381 aidB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198443 17989016 BMEII0671 NP_541649.1 ACYL-COA DEHYDROGENASE Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Repair (Delrue et al., 2004).

FUNCTION: Protection against alkylation damage to DNA (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1382 rbsC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198473 17989046 BMEII0701 NP_541679.1 RIBOSE TRANSPORT SYSTEM PERMEASE PROTEIN RBSC Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (Delrue et al., 2004).

FUNCTION: ABC transporter (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1383 cydB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198531 17989104 BMEII0759 NP_541737.1 CYTOCHROME D UBIQUINOL OXIDASE SUBUNIT II Virulence factor MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice (Endley et al., 2001). The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment (Kim et al., 2003). 11274104 12761078
1384 cydC from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198533 17989106 BMEII0761 NP_541739.1 TRANSPORT ATP-BINDING PROTEIN CYDC Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Cytochrome oxidase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1385 cydD from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198534 17989107 BMEII0762 NP_541740.1 TRANSPORT ATP-BINDING PROTEIN CYDD Virulence factor MUTATION: The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment (Kim et al., 2003). 12761078
1386 ssuB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198571 17989144 BMEII0799 NP_541777.1 NITRATE TRANSPORT PERMEASE PROTEIN NRTB Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (Delrue et al., 2004).

FUNCTION: Permease (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
14979322
1387 glpK from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198595 17989168 BMEII0823 NP_541801.1 GLYCEROL KINASE Virulence factor FUNCTION: Key enzyme in the regulation of glycerol uptake and metabolism(UniProt: Q8FWK8).

CATALYTIC ACTIVITY: ATP + glycerol = ADP + sn-glycerol 3-phosphate(UniProt: Q8FWK8).

PATHWAY: Glycerol utilization; first (rate-limiting) step(UniProt: Q8FWK8).

SIMILARITY: Belongs to the FGGY kinase family(UniProt: Q8FWK8).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1388 xfp from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198653 17989226 BMEII0881 NP_541859.1 putative phosphoketolase Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Degradation (Delrue et al., 2004).

FUNCTION: Lys. degradation (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1389 manB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198671 17989244 BMEII0899 NP_541877.1 PHOSPHOMANNOMUTASE Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1390 wbpW from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198672 17989245 BMEII0900 NP_541878.1 MANNOSE-6-PHOSPHATE ISOMERASE / MANNOSE-1-PHOSPHATE GUANYLYL TRANSFERASE (GDP) Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (Delrue et al., 2004).

FUNCTION: O-chain biosynthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1391 BMEII0923 Brucella 1198695 17989268 BMEII0923 NP_541901.1 SPERMIDINE/PUTRESCINE-BINDING PERIPLASMIC PROTEIN Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (Delrue et al., 2004).

FUNCTION: ABC transporter (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1392 nrdI Brucella melitensis bv. 1 str. 16M 1198703 17989276 BMEII0931 GG703779 NP_541909 ribonucleotide reductase stimulatory protein Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Ribonucleotide recuctase (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction, HeLa, but not in Macrophages (Delrue et al., 2004).
14979322
1393 nrdH from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198704 17989277 BMEII0932 NP_541910.1 GLUTAREDOXIN Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Ribonucleotide recuctase (Delrue et al., 2004).

MUTATION: Attenuated in HeLa, but not in Macrophages, mice (Delrue et al., 2004).
14979322
1394 BMEII0935 Brucella 1198707 17989280 BMEII0935 NP_541913.1 NICKEL RESISTANCE PROTEIN Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: Bacterial protein of unknown function (DUF89) (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1395 narG from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198722 17989295 BMEII0950 NP_541928.1 NITRATE REDUCTASE ALPHA CHAIN Virulence factor MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate (Kohler et al., 2002). A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis xx gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). 12438693
1396 norE from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198773 17989346 BMEII1001 NP_541979.1 NORE PROTEIN Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Nitric oxide reduction (Delrue et al., 2004).

MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (Delrue et al., 2004).
14979322
1397 BMEII1037 Brucella 1198809 17989382 BMEII1037 NP_542015.1 ZINC PROTEASE Virulence factor FUNCTIONAL GROUP: Other genes (Delrue et al., 2004).

FUNCTION: Zinc protease (Delrue et al., 2004).

MUTATION: Attenuated in Mice (Delrue et al., 2004).
14979322
1398 BMEII1045 Brucella 1198817 17989390 BMEII1045 NP_542023.1 HAD superfamily protein involved in N-acetyl-glucosamine catabolism Virulence factor FUNCTIONAL GROUP: Unkown function (Delrue et al., 2004).

FUNCTION: haloacid dehalogenase-like hydrolase domain (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1399 gluP from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198825 17989398 BMEII1053 NP_542031.1 GLUCOSE/GALACTOSE TRANSPORTER Virulence factor FUNCTION: Intake of glucose and galactose (Potential)(UniProt: Q8YB48).

SUBCELLULAR LOCATION: Inner membrane; multi-pass membrane protein (Probable)(UniProt: Q8YB48).

SIMILARITY: Belongs to the major facilitator superfamily. FHS transporter (TC 2.A.1.7) family(UniProt: Q8YB48).

MUTATION: B suis and maybe B canis seem to have two glucosegalactose transporters: gluP and gguAB. B abortus may express only gluP, which may explain why gluP mutants fail to survive long periods in the mouse (Essenberg et al., 2002).
12414147
1400 gntR from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198838 17989411 BMEII1066 NP_542044.1 PYRUVATE DEHYDROGENASE COMPLEX REPRESSOR Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Transcriptional regulator (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
14979322
1401 flgI from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198856 17989429 BMEII1084 NP_542062.1 flagellar basal body P-ring protein Virulence factor FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (Delrue et al., 2004).

FUNCTION: P-ring (Delrue et al., 2004).

MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (Delrue et al., 2004).
14979322
1402 deoR from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198865 17989438 BMEII1093 NP_542071.1 GLYCEROL-3-PHOSPHATE REGULON REPRESSOR Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Transcriptional regulator (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1403 gtrB from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198873 17989446 BMEII1101 NP_542079.1 BACTOPRENOL GLUCOSYL TRANSFERASE / BACTOPRENOL APOLIPOPROTEIN N-ACYLTRANSFERASE Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: glycosyl transerase (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages (Delrue et al., 2004).
14979322
1404 vjbR from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198888 17989461 BMEII1116 NP_542094.1 TRANSCRIPTIONAL ACTIVATOR, LUXR FAMILY Virulence factor FUNCTIONAL GROUP: Regulation (Delrue et al., 2004).

FUNCTION: Transcriptional regulator (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1405 gnd from Brucella melitensis bv. 1 str. 16M Brucella melitensis bv. 1 str. 16M 1198896 17989469 BMEII1124 NP_542102.1 6-phosphogluconate dehydrogenase Virulence factor MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model (Kim et al., 2003). 12761078
1704 metH from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3786978 82699102 BAB1_0188 YP_413676.1 B12-dependent methionine synthase Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Met. synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, HeLa (Delrue et al., 2004).
14979322
1705 pgi from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3787092 82699210 BAB1_0316 YP_413784.1 glucose-6-phosphate isomerase Virulence factor CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(UniProt: Q8G2N3).

PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 2(UniProt: Q8G2N3).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G2N3).

SIMILARITY: Belongs to the GPI family(UniProt: Q8G2N3).

MUTATION: B. suis pgi is a gene identified by signature-tagged mutagenesis. The mutant is attenuated inside THP1 macrophages. The mutation of the pgi gene could also affect the biosynthesis of the bacterial peptidoglycan (Foulongne et al., 2000).
10678941
1706 tig from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3787589 82699768 BAB1_0917 YP_414342.1 trigger factor Virulence factor FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(UniProt: Q8G129).

SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(UniProt: Q8G129).

SIMILARITY: Contains 1 PPIase FKBP-type domain(UniProt: Q8G129).

MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice (Lestrate et al., 2003).
14638795
1707 uvrA from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3787776 82699947 BAB1_1128 YP_414521.1 excinuclease ABC subunit A Virulence factor FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(UniProt: Q8G0I9).

SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(UniProt: Q8G0I9).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G0I9).

SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(UniProt: Q8G0I9).

SIMILARITY: Contains 2 ABC transporter domains(UniProt: Q8G0I9).

MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants (Roux et al., 2006).
16816190
1708 miaA from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3787973 82700207 BAB1_1409 YP_414781.1 tRNA delta(2)-isopentenylpyrophosphate transferase Virulence factor FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(UniProt: Q8CY40).

CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(UniProt: Q8CY40).

SIMILARITY: Belongs to the IPP transferase family(UniProt: Q8CY40).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
12438693
1709 aroC from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788622 82699340 BAB1_0454 YP_413914.1 chorismate synthase Virulence factor CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(UniProt: P63608).

COFACTOR: Reduced flavin (By similarity)(UniProt: P63608).

PATHWAY: Metabolic intermediate biosynthesis; chorismate biosynthesis; chorismate from D-erythrose 4-phosphate and PEP: step 7 [final step](UniProt: P63608).

PATHWAY: Context: Aromatic amino acids biosynthesis(UniProt: P63608).

SUBUNIT: Homotetramer (By similarity)(UniProt: P63608).

SIMILARITY: Belongs to the chorismate synthase family(UniProt: P63608).

MUTATION: The cloned aroC gene complements Escherichia coli and Salmonella enterica serovar Typhimurium aroC mutants. A B suis aroC mutant was found to be unable to grow in a defined medium without aromatic compounds. The mutant was highly attenuated in it issue culture (THP1 macrophages and HeLa cells) and murine virulence models (Foulongne et al., 2001).
11119550
1710 aspC from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788626 82700306 BAB1_1514 YP_414880.1 aspartate aminotransferase Virulence factor MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth (Kim et al., 2003). 12761078
1711 bacA from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788635 82699288 BAB1_0402 YP_413862.1 transport protein Virulence factor MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain (LeVier et al., 2000). R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis (LeVier et al., 2000). The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria(LeVier et al., 2000). 10741969
1712 cysI from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788677 82699095 BAB1_0181 YP_413669.1 Nitrite/sulfite reductase ferredoxin-like half domain:Nitrite and sulfite reductase iron-sulfur/siroheme-binding site:Nitrite... Virulence factor FUNCTIONAL GROUP: Oxidoreduction (Delrue et al., 2004).

FUNCTION: Sulfite reductate (Delrue et al., 2004).

MUTATION: Attenuated in Mice, Macrophages, but not in HeLa (Delrue et al., 2004).
14979322
1713 dut from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788687 82700463 BAB1_1687 YP_415037.1 deoxyuridine 5'-triphosphate nucleotidohydrolase Virulence factor FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(UniProt: P64005).

CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(UniProt: P64005).

PATHWAY: De novo synthesis of thymidylate(UniProt: P64005).

SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). the dUTPase family(UniProt: P64005).
12438693
1714 glnA from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788725 82699855 BAB1_1023 YP_414429.1 Glutamine synthetase class-I, adenylation site:Glutamine synthetase type I:Glutamine synthetase, catalytic domain:Glutamine s... Virulence factor MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). 12438693
1715 gloA from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788728 82700098 BAB1_1286 YP_414672.1 Glyoxalase/Bleomycin resistance protein/dioxygenase domain:Glyoxalase I Virulence factor FUNCTIONAL GROUP: a.a. metabolism, Unkown (Delrue et al., 2004).

FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) (Delrue et al., 2004).

MUTATION: Attenuated in Differential fluorescence induction (Delrue et al., 2004).
14979322
1716 glyA from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788734 82699646 BAB1_0787 YP_414220.1 serine hydroxymethyltransferase Virulence factor FUNCTION: Interconversion of serine and glycine(UniProt: Q8G1F1).

CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(UniProt: Q8G1F1).

COFACTOR: Pyridoxal phosphate (By similarity)(UniProt: Q8G1F1).

PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(UniProt: Q8G1F1).

SUBUNIT: Homotetramer (By similarity)(UniProt: Q8G1F1).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G1F1).

SIMILARITY: Belongs to the SHMT family(UniProt: Q8G1F1).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
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1717 gmd from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788735 82699425 BAB1_0545 YP_413999.1 Short-chain dehydrogenase/reductase SDR:GDP-mannose 4,6-dehydratase Virulence factor MUTATION: gmd may be involved in perosamine synthesis. It has been shown to be in LPS synthesis since its B. melitensis mutation induces rough phenotype (Moriyón et al., 2004). 15099501
1718 hfq from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788748 82699953 BAB1_1134 YP_414527.1 RNA-binding protein Hfq Virulence factor FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(UniProt: P0A3G8).

SIMILARITY: Belongs to the hfq family(UniProt: P0A3G8).

MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source(Sonnleitner et al., 2003).

hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages (Roop et al., 2003).

In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication (Roop et al., 2003).

A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type (Roop et al., 2003).
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1719 hisC from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788751 82700747 BAB1_1988 YP_415321.1 histidinol-phosphate aminotransferase Virulence factor CATALYTIC ACTIVITY: L-histidinol phosphate + 2-oxoglutarate = 3-(imidazol-4-yl)-2-oxopropyl phosphate + L-glutamate(UniProt: Q8FY98).

COFACTOR: Pyridoxal phosphate (By similarity)(UniProt: Q8FY98).

PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 7(UniProt: Q8FY98).

SUBUNIT: Homodimer (By similarity)(UniProt: Q8FY98).

SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family. Histidinol-phosphate aminotransferase subfamily(UniProt: Q8FY98).

MUTATION: hisC encodes for histidinol phosphate transaminase. Brucella hisC mutant showed very little reduction in number by 2 weeks post-inoculation, but was reduced by 8 weeks.
1720 hisD Brucella 3788752 82699185 BAB1_0285 YP_413759.1 histidinol dehydrogenase Virulence factor FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(UniProt: Q8G2R2).

CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(UniProt: Q8G2R2).

COFACTOR: Binds 1 zinc ion per subunit (By similarity)(UniProt: Q8G2R2).

PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 9 [final step](UniProt: Q8G2R2).

SIMILARITY: Belongs to the histidinol dehydrogenase family(UniProt: Q8G2R2).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis hisD gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
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1721 hisF from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788754 82700840 BAB1_2086 YP_415414.1 imidazole glycerol phosphate synthase subunit HisF Virulence factor FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(UniProt: Q8FY07).

CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(UniProt: Q8FY07).

PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 5(UniProt: Q8FY07).

SUBUNIT: Heterodimer of hisH and hisF (By similarity)(UniProt: Q8FY07).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8FY07).

SIMILARITY: Belongs to the hisA/hisF family(UniProt: Q8FY07).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis hisF gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
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1722 hpt from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788755 82700745 BAB1_1986 YP_415319.1 Phosphoribosyltransferase:Hypoxanthine phosphoribosyl transferase Virulence factor FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis (Delrue et al., 2004).

FUNCTION: Purines synthesis (Delrue et al., 2004).

MUTATION: Attenuated in Macrophages, HeLa (Delrue et al., 2004).
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1723 ilvD from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788763 82699018 BAB1_0096 YP_413592.1 dihydroxy-acid dehydratase Virulence factor CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(UniProt: Q8G353).

COFACTOR: Binds 1 4Fe-4S cluster (Potential)(UniProt: Q8G353).

PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-isoleucine from 2-oxobutanoate: step 3(UniProt: Q8G353).

PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from pyruvate: step 3(UniProt: Q8G353).

SIMILARITY: Belongs to the ilvD/edd family(UniProt: Q8G353).

MUTATION: Of those B abortus mutants with mini-Tn5 insertions in genes predicted to be involved in amino acid biosynthesis and transport, only the ilvD mutant, displayed attenuation in both macrophages and mice. The othre two amino acid biosynthesis mutants [trpB::miniTn5 and pheA::miniTn5] displayed wild-type virulence in mice but attenuated inside macrophages. The studies with B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not (Alcantara et al., 2004).
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1724 leuA from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788771 162002872 BAB1_1583 YP_414947.2 2-isopropylmalate synthase Virulence factor FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(UniProt: Q8FZC4).

CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(UniProt: Q8FZC4).

PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 1(UniProt: Q8FZC4).

SUBUNIT: Homotetramer (By similarity)(UniProt: Q8FZC4).

SIMILARITY: Belongs to the alpha-IPM synthetase/homocitrate synthase family. LeuA type 2 subfamily(UniProt: Q8FZC4).

MUTATION: leuA is a B. suis gene identified by signature-tagged mutagenesis. It is attenuated inside THP1 macrophage cell line.
1725 leuC from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788772 82700673 BAB1_1905 YP_415247.1 isopropylmalate isomerase large subunit Virulence factor FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(UniProt: Q8FYG9).

CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(UniProt: Q8FYG9).

CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(UniProt: Q8FYG9).

COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(UniProt: Q8FYG9).

PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 2(UniProt: Q8FYG9).

SUBUNIT: Heterodimer of leuC and leuD (By similarity)(UniProt: Q8FYG9).

SIMILARITY: Belongs to the aconitase/IPM isomerase family. LeuC type 1 subfamily(UniProt: Q8FYG9).

MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis leuC gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002).
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1726 lysA from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788788 82700743 BAB1_1984 YP_415317.1 Orn/DAP/Arg decarboxylase, family 2:ATP/GTP-binding site motif A (P-loop):Diaminopimelate decarboxylase Virulence factor MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells (Kohler et al., 2002). 12438693
1727 ntrC from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788817 82699958 BAB1_1140 YP_414532.1 CbxX/CfqX superfamily:Response regulator receiver:Sigma-54 factor interaction domain:Helix-turn-helix, Fis-type:AAA ATPase Virulence factor MUTATION: ntrC encodes for a response regulator subfamily (NtrC). A B suis ntrC isogenic mutant was constructed which showed no significant differences in growth rates compared to the wild-type strain when grown at different temperatures in vitro. However, the mutant exhibited a reduction in metabolic activity in the presence of many amino acids. The mutation did not affect survival or multiplication of B suis in macrophages, but during the initial stages of infection in the murine brucellosis model, the ntrC mutant showed a reduced ability to multiply rapidly in splenic tissue (Dorrell et al., 1999). 10373105
1728 ntrY from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788818 82699957 BAB1_1139 YP_414531.1 PAS domain:ATP-binding region, ATPase-like:Histidine kinase, HAMP region:Histidine kinase A, N-terminal:Bacterial sensor prot... Virulence factor MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype (Foulongne et al., 2000). 10678941
1729 omp19 from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788831 82700695 BAB1_1930 YP_415269.1 lipoprotein Omp19 Virulence factor SUBCELLULAR LOCATION: Outer membrane; lipid-anchor(UniProt: P0A3P2).

MISCELLANEOUS: Elicits an immune response in humans, mice, sheep and goats infected with B.melitensis or B.abortus, but not in B.abortus-infected cattle(UniProt: P0A3P2).

SIMILARITY: Belongs to the rhizobiaceae omp19 lipoprotein family(UniProt: P0A3P2).

MUTATION: Omp19 is an immunoreactive outer membrane lipoprotein. Significantly fewer brucellae were recovered from the spleens of mice infected with the omp19 mutant than from those of mice infected with the parent strain at 4 and 8 weeks postinfection. The omp19 mutant exhibited an increase in sensitivity to the polycation polymyxin B and to sodium deoxycholate. These results indicate that inactivation of the omp19 gene alters the outer membrane properties of B abortus (Tibor et al., 2002).
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1730 pepN from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788843 82699509 BAB1_0641 YP_414083.1 Membrane alanine aminopeptidase:Neutral zinc metallopeptidase, zinc-binding region Virulence factor MUTATION: A single mutation of PepN leads to a significant decrease in the growth rate, thus PepN seems to play a more prominent role than do the other proteases (Contreras-Rodriguez et al., 2003). 12933870
1731 pgm from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788847 82698981 BAB1_0055 YP_413555.1 phosphoglucomutase Virulence factor MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells (Ugalde et al., 2000).

B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro (Ugalde et al., 2000).
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1732 pheA from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788850 82698963 BAB1_0034 YP_413537.1 prephenate dehydratase Virulence factor MUTATION: The product of pheA gene is specifically dedicated to the biosynthesis of phenylalanine. The B. abortus pheA mutant with mini-Tn5 disruption displays nutritional defects in vitro. Experimental findings with the B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not. The pheA::miniTn5 mutant displayed attenuation in macrophages but not in mice (Alcantara et al., 2004). 15271960
1733 pth from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788869 82700344 BAB1_1552 YP_414918.1 peptidyl-tRNA hydrolase Virulence factor FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(UniProt: P65864).

CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(UniProt: P65864).

SUBUNIT: Monomer (By similarity)(UniProt: P65864).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: P65864).

SIMILARITY: Belongs to the PTH family(UniProt: P65864).

MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed (Danese et al., 2004).
15385478
1734 purD from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788874 82699328 BAB1_0442 YP_413902.1 phosphoribosylamine--glycine ligase Virulence factor CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(UniProt: Q8G2B1).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; N(1)-(5-phospho-D-ribosyl)glycinamide from 5-phospho-alpha-D-ribose 1-diphosphate: step 2(UniProt: Q8G2B1).

PATHWAY: Context: Purine biosynthesis(UniProt: Q8G2B1).

SIMILARITY: Belongs to the GARS family(UniProt: Q8G2B1).

SIMILARITY: Contains 1 ATP-grasp domain(UniProt: Q8G2B1).

MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages (Drazek et al., 1995).

Like the purE mutant, a purD::Tn10 mutant has reduced survival in murine macrophages and reduced virulence in mice (Drazek et al., 1995).
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1735 purF from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788875 82699358 BAB1_0472 YP_413932.1 amidophosphoribosyltransferase Virulence factor MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth (Kim et al., 2003). 12761078
1736 purH from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788876 82700596 BAB1_1824 YP_415170.1 bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase Virulence factor CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(UniProt: P67540).

CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(UniProt: P67540).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (10-formyl THF route): single step(UniProt: P67540).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide: single step [final step](UniProt: P67540).

PATHWAY: Context: Purine biosynthesis(UniProt: P67540).

DOMAIN: The IMP cyclohydrolase activity resides in the N-terminal region (By similarity)(UniProt: P67540).

SIMILARITY: Belongs to the purH family(UniProt: P67540).

MUTATION: B. abortus mutant with mini-Tn5-disrupted purH displays nutritional defects in vitro (Alcantara et al., 2004).
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1737 purM from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788878 82699599 BAB1_0731 YP_414173.1 phosphoribosylaminoimidazole synthetase Virulence factor CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(UniProt: Q8G1K5).

PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 2(UniProt: Q8G1K5).

PATHWAY: Context: Purine biosynthesis(UniProt: Q8G1K5).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: Q8G1K5).

SIMILARITY: Belongs to the AIR synthase family(UniProt: Q8G1K5).

MUTATION: B. abortus purM gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study (Kim et al., 2003).
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1738 purN from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788879 162002876 BAB1_0730 YP_414172.2 phosphoribosylglycinamide formyltransferase Virulence factor MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study (Kim et al., 2003). 12761078
1739 pyc from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788880 82700564 BAB1_1791 YP_415138.1 pyruvate carboxylase Virulence factor MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages (Foulongne et al., 2000). 10678941
1740 pyrD from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788883 82699235 BAB1_0341 YP_413809.1 dihydroorotate dehydrogenase 2 Virulence factor MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth (Kim et al., 2003). 12761078
1741 recA from Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 3788897 82700036 BAB1_1224 YP_414610.1 recombinase A Virulence factor FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(UniProt: P65976).

SUBCELLULAR LOCATION: Cytoplasm (By similarity)(UniProt: P65976).

SIMILARITY: Belongs to the recA family(UniProt: P65976).

MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice (Tatum et al., 1993).

The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persis