| 1 |
aidB |
I: Lipid transport and metabolism |
Yes |
FUNCTIONAL GROUP: DNA/RNA metabolism, Repair (PubMed: 14979322).
FUNCTION: Protection against alkylation damage to DNA (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 2 |
alkA |
L: Replication, recombination and repair |
Yes |
FUNCTIONAL GROUP: DNA/RNA metabolism, Repair (PubMed: 14979322).
FUNCTION: HhH-GPD superfamily base excision DNA repair (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 3 |
amiC |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan (PubMed: 14979322).
FUNCTION: Cell-wall hydrolysis (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 4 |
ansC |
K: Transcription |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (PubMed: 14979322).
FUNCTION: Transcriptional regulator (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 5 |
araG |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Transport (PubMed: 14979322).
FUNCTION: L-arabinose transport (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages (PubMed: 14979322). |
| 6 |
aroC |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): Chorismate synthase (EC 4.2.3.5) (5-enolpyruvylshikimate-3-phosphate phospholyase)(Swiss-prot: P63608).
CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(Swiss-prot: P63608).
COFACTOR: Reduced flavin (By similarity)(Swiss-prot: P63608).
PATHWAY: Metabolic intermediate biosynthesis; chorismate biosynthesis; chorismate from D-erythrose 4-phosphate and PEP: step 7 [final step](Swiss-prot: P63608).
PATHWAY: Context: Aromatic amino acids biosynthesis(Swiss-prot: P63608).
SUBUNIT: Homotetramer (By similarity)(Swiss-prot: P63608).
SIMILARITY: Belongs to the chorismate synthase family(Swiss-prot: 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 (PubMed: 11119550). |
| 7 |
arsR6 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: ArsR family (PubMed: 16113274).
MUTATION: Attenuated in mice (PubMed: 16113274). |
| 8 |
artI |
T: Signal transduction mechanisms |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Transport (PubMed: 14979322).
FUNCTION: Arginine transport system (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction (PubMed: 14979322). |
| 9 |
aspB |
K: Transcription |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: Aminotransferase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 10 |
aspC |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): aspartate aminotransferase
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 (PubMed: 12761078). |
| 11 |
bacA |
I: Lipid transport and metabolism |
Yes |
Protein name(s): bacteroid development protein BacA
MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain (PubMed: 10741969). R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis (PubMed: 10741969). 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(PubMed: 12270820). |
| 12 |
bcsP31 |
N/A
|
No |
Protein name(s): 31 kDa immunogenic protein precursor(Swiss-prot: P0A3T2).
MISCELLANEOUS: Brucella abortus is the causative agent for brucellosis in cattle and man(Swiss-prot: P0A3T2).
MUTATION: The 31-kDa salt-extractable immunogenic protein, BCSP31, was deleted from several Brucella abortus
strains by replacement with a marker gene encoding resistance to the antibiotics kanamycin and neomycin. The BCSP31 gene replacement plasmids, constructed with ColEl-derived vectors, were introduced by electroporation into B. abortus strain 19 (S19), into a rough variant of B. abortus S19, and into B. abortus S2308, and antibiotic-resistant transformants were isolated. Loss of
the gene encoding BCSP31 and presence of the marker gene were confirmed by Southern analysis. Vector
sequences were either absent or linked to the genome, indicating that ColEl-derived plasmids are not
maintained in B. abortus. Survival of B. abortus mutant strains in the macrophagelike cell line J774 and in HeLa cells was examined and shown to be indistinguishable from that of the parental strain (PubMed: 1937745). |
| 13 |
bfr |
P: Inorganic ion transport and metabolism |
No |
Protein name(s): Bacterioferritin (BFR)(Swiss-prot: Q8FW95).
FUNCTION: May perform analogous functions in iron detoxification and storage to that of animal ferritins(Swiss-prot: Q8FW95).
COFACTOR: Binds 1 heme B (iron-protoporphyrin IX) group per dimer (By similarity)(Swiss-prot: Q8FW95).
SUBUNIT: Oligomer of 24 identical subunits (By similarity)(Swiss-prot: Q8FW95).
MISCELLANEOUS: The di-iron binding site functions as active site where iron ions are oxidized from Fe(2+) to Fe(3+) before they are stored (By similarity)(Swiss-prot: Q8FW95).
SIMILARITY: Belongs to the bacterioferritin family(Swiss-prot: Q8FW95).
SIMILARITY: Contains 1 ferritin-like diiron domain(Swiss-prot: Q8FW95).
MUTATION: Brucella bacterioferritin (BFR) is a heme -containing iron storage multimeric protein composed of 24 identical subunits, which form a roughly spherical protein shell surrounding a central iron storage cavity. A BFR deletion mutant of Brucella melitensis 16M was generated by gene replacement. The deletion was complemented with a broad -host- range vector carrying the wild-type bfr gene , pBBR-bfr. The survival and growth of the mutant, B melitensis PAD 2- 78, were similar to those of its parental strain in human monocyte -derived macrophages (MDM). These results suggest that BFR is not essential for the intracellular survival of B melitensis in human MDM (PubMed: 9317046). |
| 14 |
bicA |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (PubMed: 14979322).
FUNCTION: Macrolide efflux (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 15 |
BMEI0085 |
-: Not in COGs |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Brucella orphan gene (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 16 |
BMEI0455 |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Glutathione S-transferase, C-terminal domain (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 17 |
BMEI0671 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Terc dome (efflux) (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 18 |
BMEI1229 |
L: Replication, recombination and repair |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Exonuclease X-T domain (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 19 |
BMEI1258 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (PubMed: 14979322).
FUNCTION: ABC transporter (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction (PubMed: 14979322). |
| 20 |
BMEI1339 |
-: Not in COGs |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Brucella/Agrobacterium orphan gene (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 21 |
BMEI1361 |
-: Not in COGs |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 22 |
BMEI1443 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: haloacid dehalogenase-like hydrolase domain (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 23 |
BMEI1448 |
T: Signal transduction mechanisms |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: EAL domain (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 24 |
BMEI1531 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: Other genes (PubMed: 14979322).
FUNCTION: protein-protein interaction (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 25 |
BMEI1658 |
-: Not in COGs |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Brucella orphan gene (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 26 |
BMEI1809 |
S: Function unknown |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: ERFK/YBIS/YCFS/YNHG family (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 27 |
BMEI1844 |
-: Not in COGs |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Domain of Unkown Function (DUF930) (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 28 |
BMEI1859 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Uncharacterised protein family 0005 (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 29 |
BMEI1879 |
-: Not in COGs |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Brucella/Mesorhizobium orphan gene (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 30 |
BMEI1902 |
H: Coenzyme transport and metabolism |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Brucella/Mesorhizobium orphan gene (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 31 |
BMEII0128 |
S: Function unknown |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Uncharacterised protein family (DUF0261) (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 32 |
BMEII0274 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: GTPase of unknown function domain, FeoB domain (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 33 |
BMEII0318 |
V: Defense mechanisms |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 34 |
BMEII0336 |
P: Inorganic ion transport and metabolism |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (PubMed: 14979322).
FUNCTION: ABC transporter (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 35 |
BMEII0626 |
E: Amino acid transport and metabolism |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Dipeptidase domain (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 36 |
BMEII0923 |
E: Amino acid transport and metabolism |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (PubMed: 14979322).
FUNCTION: ABC transporter (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 37 |
BMEII0935 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Bacterial protein of unknown function (DUF89) (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 38 |
BMEII1037 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: Other genes (PubMed: 14979322).
FUNCTION: Zinc protease (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 39 |
BMEII1045 |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: haloacid dehalogenase-like hydrolase domain (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 40 |
bp26 |
N/A
|
No |
Protein name(s): 26 kDa periplasmic immunogenic protein precursor (28 kDa outer membrane protein) (28 kDa cytosoluble protein) (CP28)(Swiss-prot: P0A3U9).
SUBCELLULAR LOCATION: Periplasmic(Swiss-prot: P0A3U9).
MUTATION: The periplasmic protein BP26 is an immunodominant antigen in the serological responses of Brucella infected animals. Cloning of the gene coding for BP26 has allowed the construction of a mutant of B abortus S19 vaccine strain unable to express bp26. This mutant vaccine strain protected mice from infection with pathogenic B abortus 2308 to a level similar to that of the parental S19 strain. The B abortus S19 bp26 mutant vaccine strain might be used in combination with a BP26-based serological test for the differential diagnosis between infected and vaccinated animals (PubMed: 12853399). B. melitensis Rev. 1 bp26 deletion mutant did not modify the kinetics of splenic infection nor the residual virulence of Rev. 1 in the BALBc mouse model. Vaccination of BALBc mice with the deletion mutant conferred significant protective immunity against B melitensis strain H38 or B ovis strain PA challenges, to the same extent as that induced by parental Rev. 1 strain. Thus, the Rev. 1 bp26 deletion mutant is a promising vaccine candidate against B melitensis and B ovis infections (PubMed: 15246618). |
| 41 |
bvrR |
T: Signal transduction mechanisms |
Yes |
Protein name(s): BvrR, DNA-binding response regulator
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 (PubMed: 16077108).
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 (PubMed: 12414153).
In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments (PubMed: 9826346).
B abortus bvrS bvrR mutants display reduced invasiveness and virulence (PubMed: 11401996).
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 (PubMed: 12414149).
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 (PubMed: 12218183).
BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly (PubMed: 12218183). |
| 42 |
bvrS |
T: Signal transduction mechanisms |
Yes |
Protein name(s): BvrS, sensor histidine kinase
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 (PubMed: 16077108).
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 (PubMed: 12414153).
In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments (PubMed: 9826346).
B abortus bvrS bvrR mutants display reduced invasiveness and virulence (PubMed: 11401996).
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 (PubMed: 12414149).
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 (PubMed: 12218183).
BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly (PubMed: 12218183). |
| 43 |
caiB |
C: Energy production and conversion |
Yes |
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: CAIB/BAIF family (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 44 |
carAB |
F: Nucleotide transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis (PubMed: 14979322).
FUNCTION: Clut. and pyr. Syntheis (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 45 |
cbbE |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: Ribulose-phosphate 3-epimerase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 46 |
ccoN |
O: Posttranslational modification, protein turnover, chaperones |
No |
Protein name(s): cytochrome c oxidase, cbb3-type, subunit I
MUTATION: The ccoN mutation of B suis had no effect on the replication of the bacteria inside human THP-1 macrophage cells. This is consistent with the absence of expression of the ccoNOQP promoter at the intracellular state (PubMed: 16239582). The ccoNOQP locus potentially encodes another high-oxygen-affinity oxidase, the cytochrome cbb3-type terminal oxidase |
| 47 |
clpA |
O: Posttranslational modification, protein turnover, chaperones |
No |
Protein name(s): ATP-dependent Clp protease, ATP-binding subunit ClpA
MUTATION: The protein ClpA belongs to a diverse group of polypeptides named ClpATPases , which are highly conserved , and which include several molecular chaperones. In intracellular infection of human THP-1 or murine J774 macrophage -like cells , the clpA null mutant and , to a lesser extent , the strain of B suis overexpressing b-clpA behaved similarly to the wild-type strain. In a murine model of infection, however, the absence of ClpA significantly increased persistence of B suis. These results showed that in B suis the highly conserved protein ClpA by itself was dispensable for intramacrophagic growth, but was involved in temperature -dependent growth regulation, and in bacterial clearance from infected BALBc mice (PubMed: 10878125). |
| 48 |
clpB |
O: Posttranslational modification, protein turnover, chaperones |
No |
Protein name(s): Chaperone clpB(Swiss-prot: Q7CEG6).
FUNCTION: Part of a stress-induced multi-chaperone system, it is involved in the recovery of the cell from heat-induced damage, in cooperation with dnaK, dnaJ and grpE. Acts before dnaK, in the processing of protein aggregates. Protein binding stimulates the ATPase activity; ATP hydrolysis unfolds the denatured protein aggregates, which probably helps expose new hydrophobic binding sites on the surface of clpB-bound aggregates, contributing to the solubilization and refolding of denatured protein aggregates by dnaK (By similarity)(Swiss-prot: Q7CEG6).
SUBUNIT: Homohexamer. The oligomerization is ATP-dependent (By similarity)(Swiss-prot: Q7CEG6).
SUBCELLULAR LOCATION: Cytoplasm (Probable)(Swiss-prot: Q7CEG6).
INDUCTION: By heat and acid shock(Swiss-prot: Q7CEG6).
DOMAIN: The N-terminal domain probably functions as a substrate-discriminating domain, recruiting aggregated proteins to the clpB hexamer and/or stabilizing bound proteins. The NBD2 domain is responsible for oligomerization, whereas the NBD1 domain stabilizes the hexamer probably in an ATP-dependent manner. The movement of the coiled-coil domain is essential for clpB ability to rescue proteins from an aggregated state, probably by pulling apart large aggregated proteins, which are bound between the coiled-coils motifs of adjacent clpB subunits in the functional hexamer (By similarity)(Swiss-prot: Q7CEG6).
SIMILARITY: Belongs to the clpA/clpB family(Swiss-prot: Q7CEG6).
MUTATION: Simultaneous inactivation of clpA and clpB resulted in a mutant that was sensitive to oxidative stress . In B suis expressing gfp , ClpA but not ClpB participated in degradation of the green fluorescent protein at 42C We concluded that ClpB was responsible for tolerance to several stresses and that the lethality caused by harsh environmental conditions may have similar molecular origins . |
| 49 |
clpP |
U: Intracellular trafficking and secretion |
No |
Protein name(s): ATP-dependent Clp protease proteolytic subunit (EC 3.4.21.92) (Endopeptidase Clp)(Swiss-prot: Q8G0I4).
FUNCTION: Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins (By similarity)(Swiss-prot: Q8G0I4).
CATALYTIC ACTIVITY: Hydrolysis of proteins to small peptides in the presence of ATP and magnesium. Alpha-casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are hydrolyzed (such as succinyl-Leu-Tyr-|-NHMec; and Leu-Tyr-Leu-|-Tyr-Trp, in which cleavage of the -Tyr-|-Leu- and -Tyr-|-Trp bonds also occurs)(Swiss-prot: Q8G0I4).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: Q8G0I4).
SIMILARITY: Belongs to the peptidase S14 family(Swiss-prot: Q8G0I4).
MUTATION: Our hypothesis was that ClpP, the major housekeeping intracellular protease of L lactis, degraded the cytoplasmic form of L7L12. pCYT:L7L12 was then introduced in a clpP mutant of NZ9000 but no significant increase was observed, suggesting that ClpP was not involved in this putative proteolysis (PubMed: 11823235). |
| 50 |
cobB |
H: Coenzyme transport and metabolism |
Yes |
Protein name(s): Cobyrinic acid A,C-diamide synthase(Swiss-prot: Q8G020).
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)(Swiss-prot: Q8G020).
PATHWAY: Cobalamin biosynthesis(Swiss-prot: Q8G020).
SIMILARITY: Belongs to the cobB/cobQ family. CobB subfamily(Swiss-prot: 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 (PubMed: 14638795). |
| 51 |
cobW |
R: General function prediction only |
Yes |
Cobalamin synthesis protein/P47K
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 (PubMed: 12438693). |
| 52 |
cydB |
C: Energy production and conversion |
Yes |
Protein name(s): cytochrome d ubiquinol oxidase, subunit II
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 (PubMed: 11274104). 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 (PubMed: 12761078). |
| 53 |
cydC |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: Cytochrome oxidase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 54 |
cydD |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
Protein name(s): ABC transporter, ATP-binding protein CydD
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 (PubMed: 12761078). |
| 55 |
cysI |
P: Inorganic ion transport and metabolism |
Yes |
Protein name(s): sulfite reductase (NADPH) hemoprotein beta-component
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: Sulfite reductate (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, but not in HeLa (PubMed: 14979322). |
| 56 |
cysK |
E: Amino acid transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis (PubMed: 14979322).
FUNCTION: Cys. synthesis (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 57 |
cysY |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: Disulfide oxidoreducate (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 58 |
dacF |
V: Defense mechanisms |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan (PubMed: 14979322).
FUNCTION: Peptidoglycan synthesis (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 59 |
dbsA |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Transport (PubMed: 14979322).
FUNCTION: Ribose transport (PubMed: 14979322).
MUTATION: Attenuated in HeLa (PubMed: 14979322). |
| 60 |
degP |
N/A
|
Yes |
Protein name(s): Probable serine protease do-like precursor (EC 3.4.21.-)(Swiss-prot: P0A3Z5).
SUBCELLULAR LOCATION: Periplasmic (Potential)(Swiss-prot: P0A3Z5).
SIMILARITY: Belongs to the peptidase S1C family(Swiss-prot: P0A3Z5).
SIMILARITY: Contains 2 PDZ (DHR) domains(Swiss-prot: P0A3Z5).
MUTATION: The DegP protease, a multifunctional chaperone and protease, has been shown to be essential for virulence in gram-negative pathogens such as Salmonella enterica serovar Typhimurium, Brucella abortus. The function of DegP in pathogenesis appears to be the degradation of damaged proteins that accumulate as a result of the initial host response to infection, which includes the release of reactive oxygen intermediates. Point mutations in residues presumed to represent two members of the catalytic triad (serine 210 and histidine 105) inactivated enzymatic activity, confirming the classification of DegP as a serine protease.
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis htrA (synonym: degP) gene is required for intracellular multiplication in human macrophage THP-1 cells (PubMed: 12438693). |
| 61 |
deoR |
K: Transcription |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Transcriptional regulator (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 62 |
dhbC |
Q: Secondary metabolites biosynthesis, transport and catabolism |
Yes |
FUNCTIONAL GROUP: Metal acquisition (PubMed: 14979322).
FUNCTION: Sideophore sysnhesis, Fe3+ uptake (PubMed: 14979322).
MUTATION: Attenuated in Pregant goat, but not in Mice, IFN-/-Mice, Macrophages, Trophoblastes (PubMed: 14979322). |
| 63 |
divK |
T: Signal transduction mechanisms |
Yes |
Protein name(s): polar differentiation response regulator
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Response regulator (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 64 |
dnaJ |
O: Posttranslational modification, protein turnover, chaperones |
No |
Protein name(s): Chaperone protein dnaJ(Swiss-prot: Q8FXX1).
FUNCTION: Participates actively in the response to hyperosmotic and heat shock by preventing the aggregation of stress-denatured proteins and by disaggregating proteins, also in an autonomous, dnaK-independent fashion. Unfolded proteins bind initially to dnaJ; upon interaction with the dnaJ-bound protein, dnaK hydrolyzes its bound ATP, resulting in the formation of a stable complex. GrpE releases ADP from dnaK; ATP binding to dnaK triggers the release of the substrate protein, thus completing the reaction cycle. Several rounds of ATP-dependent interactions between dnaJ, dnaK and grpE are required for fully efficient folding. Also involved, together with dnaK and grpE, in the DNA replication of plasmids through activation of initiation proteins (By similarity)(Swiss-prot: Q8FXX1).
COFACTOR: Binds 2 zinc ions per monomer (By similarity)(Swiss-prot: Q8FXX1).
SUBUNIT: Homodimer (By similarity)(Swiss-prot: Q8FXX1).
SUBCELLULAR LOCATION: Cytoplasm (Probable)(Swiss-prot: Q8FXX1).
DOMAIN: The J domain is necessary and sufficient to stimulate dnaK ATPase activity. Zinc center 1 plays an important role in the autonomous, dnaK-independent chaperone activity of dnaJ. Zinc center 2 is essential for interaction with dnaK and for dnaJ activity (By similarity)(Swiss-prot: Q8FXX1).
SIMILARITY: Belongs to the dnaJ family(Swiss-prot: Q8FXX1).
SIMILARITY: Contains 1 CR domain(Swiss-prot: Q8FXX1).
SIMILARITY: Contains 1 J domain(Swiss-prot: Q8FXX1).
MUTATION: dnaJ is located downstream of dnaK and forms an operon with dnaK. dnaJ is not involved in resistance to acid stress and intracellular multiplication of the pathogen. A dnaJ knockout mutant of B suis behaves like the wild-type strain (PubMed: 11854256). Insertional inactivation of dnaK and dnaJ within the dnaKJ locus led to the conclusion that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. 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 (PubMed: 8793869). |
| 65 |
dnaK |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
Protein name(s): Chaperone protein dnaK (Heat shock protein 70) (Heat shock 70 kDa protein) (HSP70)(Swiss-prot: Q8FXX2).
FUNCTION: Acts as a chaperone (By similarity)(Swiss-prot: Q8FXX2).
INDUCTION: By stress conditions e.g. heat shock (By similarity)(Swiss-prot: Q8FXX2).
SIMILARITY: Belongs to the heat shock protein 70 family(Swiss-prot: 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 (PubMed: 11854256).
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 (PubMed: 8793869). |
| 66 |
dppA |
E: Amino acid transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Transport (PubMed: 14979322).
FUNCTION: Dipeptide uptake (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 67 |
dsbA |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: Disulfide bond formation protein (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 68 |
dsbB |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: Disulfide bond formation protein (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages (PubMed: 14979322). |
| 69 |
dut |
F: Nucleotide transport and metabolism |
Yes |
Protein name(s): Deoxyuridine 5'-triphosphate nucleotidohydrolase (EC 3.6.1.23) (dUTPase) (dUTP pyrophosphatase)(Swiss-prot: P64005).
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)(Swiss-prot: P64005).
CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(Swiss-prot: P64005).
PATHWAY: De novo synthesis of thymidylate(Swiss-prot: 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 (PubMed: 12438693). the dUTPase family(Swiss-prot: P64005). |
| 70 |
dxps |
I: Lipid transport and metabolism |
Yes |
FUNCTIONAL GROUP: Vitamines cofactors (PubMed: 14979322).
FUNCTION: Thiamine synthesis (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction (PubMed: 14979322). |
| 71 |
entC |
Q: Secondary metabolites biosynthesis, transport and catabolism |
No |
Protein name(s): isochorismate synthase
MUTATION: 2, 3-Dihydroxybenzoic acid (DHBA ) is the only siderophore described for Brucella , and previous studies suggested that DHBA might contribute to the capacity of these organisms to persist in host macrophages. Employing an isogenic siderophore mutant (entC) constructed from virulent Brucella abortus 2308, however, it was found that production of DHBA is not required for replication in cultured murine macrophages or for the establishment and maintenance of chronic infection in the BALBc mouse model (PubMed: 10225929). |
| 72 |
entE |
Q: Secondary metabolites biosynthesis, transport and catabolism |
No |
Protein name(s): 2,3-dihydroxybenzoate-AMP ligase
MUTATION: B abortus entE mutant was unable to synthesize brucebactin, but it exhibited no defeat in intracellular infection (PubMed: 15385478). |
| 73 |
eryA |
G: Carbohydrate transport and metabolism |
No |
Protein name(s): erythritol kinase
MUTATION: EryA is an erythritol kinase. 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 (PubMed: 10708387).
The eryA gene of the bacterial pathogen Brucella abortus expressed in Escherichia coli. The resultant EryA was shown to catalyze the ATP-dependent conversion of erythritol to L-erythritol-4-phosphate (L-E4P) (PubMed: 12639570).
|
| 74 |
eryB |
C: Energy production and conversion |
Yes |
Protein name(s): erythritol phosphate dehydrogenase
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 (PubMed: 10708387).
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 (PubMed: 16177356). |
| 75 |
eryC |
-: Not in COGs |
Yes |
Protein name(s): D-erythrulose-1-phosphate dehydrogenase
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 (PubMed: 10708387).
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 (PubMed: 16177356). |
| 76 |
eryD |
K: Transcription |
No |
Protein name(s): erythritol transcriptional regulator
MUTATION: The EryA protein is the erythritol kinase, and EryB and EryC are the two dehydrogenases in the catabolic chain. EryD is a transcriptional repressor, inactivated by erythritol binding
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 (PubMed: 10708387). Sequence analysis and comparison showed that EryD was a protein with a helixturnhelix motif and probably possessed some regulatory function . To obtain further evidence for this, we constructed an eryD mutant (FJS-2) and compared the levels of ery transcription in this mutant and a wild-type strain. Transcription from the ery promoter (P1) was more active in both the mutant FJS-2 and strain B19 than in strain 2308. This result strongly suggested a repressor function for EryD (PubMed: 10708387). |
| 77 |
exbB |
U: Intracellular trafficking and secretion |
No |
Protein name(s): biopolymer transport protein ExbB
MUTATION: ExbB is part of the Ton complex , and DstC is a permease homologue of an iron ( III ) ABC transporter; in gram -negative bacteria these two complexes are involved in the uptake of iron through the outer and inner membranes, respectively. DugA is a new partner in iron utilization that exhibits homology with the bacterial conserved GTPase YchF. Analysis of these three mutants indicated that the ExbB, DstC, and DugA proteins are required for optimal assimilation of DHBA andor citrate (PubMed: 15385478). The exbB, dstC, and pthdugA mutants were not attenuated in the BALBc mice after i. p. infection (PubMed: 15385478). |
| 78 |
exsA |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Transport (PubMed: 14979322).
FUNCTION: ABC transporter (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 79 |
fbpA |
P: Inorganic ion transport and metabolism |
Yes |
FUNCTIONAL GROUP: Metal acquisition (PubMed: 14979322).
FUNCTION: Fe3+ binding (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction (PubMed: 14979322). |
| 80 |
fdhA |
C: Energy production and conversion |
Yes |
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: Formate dehydrogenase (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 81 |
feuP |
T: Signal transduction mechanisms |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Response regulator (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages (PubMed: 14979322). |
| 82 |
feuQ |
T: Signal transduction mechanisms |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Histidine kinase (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 83 |
flgE |
N: Cell motility |
Yes |
Protein name(s): Flagellar hook protein FlgE(Swiss-prot: Q8FUS9).
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (PubMed: 14979322).
FUNCTION: Hook (PubMed: 14979322).
SIMILARITY: Belongs to the flagella basal body rod proteins family(Swiss-prot: Q8FUS9).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (PubMed: 14979322). |
| 84 |
flghA |
U: Intracellular trafficking and secretion |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (PubMed: 14979322).
FUNCTION: Export apparatus (PubMed: 14979322).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (PubMed: 14979322). |
| 85 |
flgI |
N: Cell motility |
Yes |
Protein name(s): flagellar P-ring protein precursor
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (PubMed: 14979322).
FUNCTION: P-ring (PubMed: 14979322).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (PubMed: 14979322). |
| 86 |
fliC |
N: Cell motility |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (PubMed: 14979322).
FUNCTION: Flagellin (PubMed: 14979322).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (PubMed: 14979322). |
| 87 |
fliF |
U: Intracellular trafficking and secretion |
Yes |
Protein name(s): Flagellar M-ring protein FliF(Swiss-prot: Q8FUS3).
FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(Swiss-prot: 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)(Swiss-prot: Q8FUS3).
SUBCELLULAR LOCATION: Inner membrane; multi-pass membrane protein (By similarity)(Swiss-prot: Q8FUS3).
SIMILARITY: Belongs to the fliF family(Swiss-prot: 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 (PubMed: 14638795). |
| 88 |
ftcR |
T: Signal transduction mechanisms |
Yes |
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 (PubMed: 17056750). |
| 89 |
galcD |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: D-galactarate dehydratase (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 90 |
galE |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: UDP-glucose 4-epimerase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 91 |
gcvP |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): Glycine dehydrogenase [decarboxylating] (EC 1.4.4.2) (Glycine decarboxylase) (Glycine cleavage system P-protein)(Swiss-prot: Q8FVU9).
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)(Swiss-prot: Q8FVU9).
CATALYTIC ACTIVITY: Glycine + H-protein-lipoyllysine = H-protein-S-aminomethyldihydrolipoyllysine + CO(2)(Swiss-prot: Q8FVU9).
COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-prot: Q8FVU9).
SUBUNIT: The glycine cleavage system is composed of four proteins: P, T, L and H (By similarity)(Swiss-prot: Q8FVU9).
SIMILARITY: Belongs to the gcvP family(Swiss-prot: Q8FVU9).
MUTATION: gcvP encodes for glycine dehydrogenase and is required for persistent infection in mouse model (PubMed: 12523983). |
| 92 |
gcvT |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): glycine cleavage system T protein
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 (PubMed: 12438693). |
| 93 |
glnA |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): glutamine synthetase, type I
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 (PubMed: 12438693). |
| 94 |
glnD |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
Protein name(s): [Protein-PII] uridylyltransferase (EC 2.7.7.59) (PII uridylyl-transferase) (Uridylyl-removing enzyme) (UTase)(Swiss-prot: Q8G312).
FUNCTION: Modifies, by uridylylation or deuridylylation the PII (glnB) regulatory protein (By similarity)(Swiss-prot: Q8G312).
CATALYTIC ACTIVITY: UTP + [protein-PII] = diphosphate + uridylyl-[protein-PII](Swiss-prot: Q8G312).
SIMILARITY: Belongs to the glnD family(Swiss-prot: 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 (PubMed: 10678941). |
| 95 |
glnL |
T: Signal transduction mechanisms |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Nitrogen regulatory IIA (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 96 |
gloA |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): lactoylglutathione lyase
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction (PubMed: 14979322). |
| 97 |
glpK |
C: Energy production and conversion |
Yes |
Protein name(s): Glycerol kinase (EC 2.7.1.30) (ATP:glycerol 3-phosphotransferase) (Glycerokinase) (GK)(Swiss-prot: Q8FWK8).
FUNCTION: Key enzyme in the regulation of glycerol uptake and metabolism(Swiss-prot: Q8FWK8).
CATALYTIC ACTIVITY: ATP + glycerol = ADP + sn-glycerol 3-phosphate(Swiss-prot: Q8FWK8).
PATHWAY: Glycerol utilization; first (rate-limiting) step(Swiss-prot: Q8FWK8).
SIMILARITY: Belongs to the FGGY kinase family(Swiss-prot: Q8FWK8).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 98 |
glt1 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis (PubMed: 14979322).
FUNCTION: Glut. sunthesis (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 99 |
gltD |
R: General function prediction only |
Yes |
Protein name(s): glutamate synthase, small subunit
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 (PubMed: 10858227). |
| 100 |
gluP |
G: Carbohydrate transport and metabolism |
Yes |
Protein name(s): Glucose/galactose transporter(Swiss-prot: Q8YB48).
FUNCTION: Intake of glucose and galactose (Potential)(Swiss-prot: Q8YB48).
SUBCELLULAR LOCATION: Inner membrane; multi-pass membrane protein (Probable)(Swiss-prot: Q8YB48).
SIMILARITY: Belongs to the major facilitator superfamily. FHS transporter (TC 2.A.1.7) family(Swiss-prot: 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 (PubMed: 12414147). |
| 101 |
glyA |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): Serine hydroxymethyltransferase (EC 2.1.2.1) (Serine methylase) (SHMT)(Swiss-prot: Q8G1F1).
FUNCTION: Interconversion of serine and glycine(Swiss-prot: Q8G1F1).
CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(Swiss-prot: Q8G1F1).
COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-prot: Q8G1F1).
PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(Swiss-prot: Q8G1F1).
SUBUNIT: Homotetramer (By similarity)(Swiss-prot: Q8G1F1).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: Q8G1F1).
SIMILARITY: Belongs to the SHMT family(Swiss-prot: 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 (PubMed: 12438693). |
| 102 |
gmd |
M: Cell wall/membrane biogenesis |
Yes |
Protein name(s): GDP-mannose 4,6-dehydratase
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 (PubMed: 15099501). |
| 103 |
gnd |
G: Carbohydrate transport and metabolism |
Yes |
Protein name(s): 6-phosphogluconate dehydrogenase
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 (PubMed: 12761078). |
| 104 |
gntR |
K: Transcription |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Transcriptional regulator (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 105 |
gntR1 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: gntR family (PubMed: 16113274).
MUTATION: Attenuated using plasmid-tagged mutagenesis method (PubMed: 16113274). |
| 106 |
gntR10 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: gntR family (PubMed: 16113274).
MUTATION: Attenuated using plasmid-tagged mutagenesis method (PubMed: 16113274). |
| 107 |
gntR17 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: gntR family (PubMed: 16113274).
MUTATION: Attenuated in mice (PubMed: 16113274). |
| 108 |
gntR2 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: gntR family (PubMed: 16113274).
MUTATION: Attenuated in mice (PubMed: 16113274). |
| 109 |
gntR4 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: gntR family (PubMed: 16113274).
MUTATION: Attenuated using plasmid-tagged mutagenesis method (PubMed: 16113274). |
| 110 |
gntR5 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: gntR family (PubMed: 16113274).
MUTATION: Attenuated using plasmid-tagged mutagenesis method (PubMed: 16113274). |
| 111 |
gpt |
N/A
|
Yes |
Protein name(s): Xanthine phosphoribosyltransferase (EC 2.4.2.22) (Xanthine-guanine phosphoribosyltransferase) (XGPRT)(Swiss-prot: Q8G0P3).
FUNCTION: Acts on guanine, xanthine and to a lesser extent hypoxanthine (By similarity)(Swiss-prot: Q8G0P3).
CATALYTIC ACTIVITY: 9-(5-phospho-beta-D-ribosyl)xanthine + diphosphate = 5-phospho-alpha-D-ribose 1-diphosphate + xanthine(Swiss-prot: Q8G0P3).
COFACTOR: Binds 1 magnesium ion per subunit (By similarity)(Swiss-prot: Q8G0P3).
COFACTOR: Binds 1 sulfate ion per subunit (By similarity)(Swiss-prot: Q8G0P3).
PATHWAY: Purine salvage(Swiss-prot: Q8G0P3).
SUBUNIT: Homotrimer (By similarity)(Swiss-prot: Q8G0P3).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: Q8G0P3).
SIMILARITY: Belongs to the purine/pyrimidine phosphoribosyltransferase family. XGPT subfamily(Swiss-prot: Q8G0P3).
MUTATION: gpt codes for hypoxanthine-guanine phosphoribosyl transferase, an enzyme of the purine nucleotide biosynthesis pathway. A transposon insertion in the B. suis gpt-like gene has an attenuated phenotype in THP-1 human macrophages. This could be related to results in other studies where many auxotrophic mutations for purine or nucleotide biosynthesis lead to attenuated strains (PubMed: 10678941). |
| 112 |
gtrB |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: glycosyl transerase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 113 |
hdeA |
-: Not in COGs |
No |
Protein name(s): hdeA protein
MUTATION: HdeA is a low pH dependent periplasmic chaperone. Although mutational analysis demonstrated that HdeA contributes to acid resistance in this bacterium , this protein is not required for wild-type virulence in the BALBc mouse model. Brucella HdeA is NCBI accession no AAR98497. The B abortus hdeA mutant MWV2 displayed an approximately 10- fold greater susceptibility to killing by exposure to pH 4 during the 30 h incubation period than did the parental 2308 strain (PubMed: 15863292). It is also important to note that loss of hdeA does not impart the same degree of acid sensitivity upon the B abortus hdeA mutant as that exhibited by the isogenic hfq mutant Hfq3 in the same assay. This latter finding argues that inefficient expression of hdeA is not the sole basis for the prominent acid sensitivity displayed by stationary phase cultures of the B abortus hfq mutant (Robertson and Roop, 1999)(PubMed: 15863292). |
| 114 |
hemH |
H: Coenzyme transport and metabolism |
Yes |
Protein name(s): Ferrochelatase (EC 4.99.1.1) (Protoheme ferro-lyase) (Heme synthetase)(Swiss-prot: P0A3D7).
FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(Swiss-prot: P0A3D7).
CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(Swiss-prot: P0A3D7).
PATHWAY: Protoheme biosynthesis; last step(Swiss-prot: P0A3D7).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: P0A3D7).
SIMILARITY: Belongs to the ferrochelatase family(Swiss-prot: 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 (PubMed: 11553564). |
| 115 |
hfq |
R: General function prediction only |
Yes |
Protein name(s): Protein hfq(Swiss-prot: P0A3G8).
FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(Swiss-prot: P0A3G8).
SIMILARITY: Belongs to the hfq family(Swiss-prot: 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(PubMed: 14521880).
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 (PubMed: 12730323).
In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication (PubMed: 15908400).
A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type (PubMed: 11173035). |
| 116 |
hisC |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): Histidinol-phosphate aminotransferase (EC 2.6.1.9) (Imidazole acetol-phosphate transaminase)(Swiss-prot: Q8FY98).
CATALYTIC ACTIVITY: L-histidinol phosphate + 2-oxoglutarate = 3-(imidazol-4-yl)-2-oxopropyl phosphate + L-glutamate(Swiss-prot: Q8FY98).
COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-prot: Q8FY98).
PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 7(Swiss-prot: Q8FY98).
SUBUNIT: Homodimer (By similarity)(Swiss-prot: Q8FY98).
SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family. Histidinol-phosphate aminotransferase subfamily(Swiss-prot: 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. |
| 117 |
hisD |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): Histidinol dehydrogenase (EC 1.1.1.23) (HDH)(Swiss-prot: Q8G2R2).
FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(Swiss-prot: Q8G2R2).
CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(Swiss-prot: Q8G2R2).
COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-prot: Q8G2R2).
PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 9 [final step](Swiss-prot: Q8G2R2).
SIMILARITY: Belongs to the histidinol dehydrogenase family(Swiss-prot: 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 (PubMed: 12438693). |
| 118 |
hisF |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): Imidazole glycerol phosphate synthase subunit hisF (EC 4.1.3.-) (IGP synthase cyclase subunit) (IGP synthase subunit hisF) (ImGP synthase subunit hisF) (IGPS subunit hisF)(Swiss-prot: Q8FY07).
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)(Swiss-prot: 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(Swiss-prot: Q8FY07).
PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 5(Swiss-prot: Q8FY07).
SUBUNIT: Heterodimer of hisH and hisF (By similarity)(Swiss-prot: Q8FY07).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: Q8FY07).
SIMILARITY: Belongs to the hisA/hisF family(Swiss-prot: 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 (PubMed: 12438693). |
| 119 |
hpt |
F: Nucleotide transport and metabolism |
Yes |
Protein name(s): hypoxanthine-guanine phosphoribosyltransferase
FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis (PubMed: 14979322).
FUNCTION: Purines synthesis (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 120 |
htrA |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: Stress proteins/Chaperones (PubMed: 14979322).
FUNCTION: Protease (PubMed: 14979322).
MUTATION: Attenuated in "Goat", Macrophages, but not in Mice (PubMed: 14979322). |
| 121 |
ilvC |
H: Coenzyme transport and metabolism |
Yes |
Protein name(s): Ketol-acid reductoisomerase (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (Alpha-keto-beta-hydroxylacil reductoisomerase)(Swiss-prot: Q8FZU1).
CATALYTIC ACTIVITY: (R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH(Swiss-prot: Q8FZU1).
CATALYTIC ACTIVITY: (2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-hydroxy-2-ethyl-3-oxobutanoate + NADPH(Swiss-prot: Q8FZU1).
PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-isoleucine from 2-oxobutanoate: step 2(Swiss-prot: Q8FZU1).
PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from pyruvate: step 2(Swiss-prot: Q8FZU1).
SIMILARITY: Belongs to the ketol-acid reductoisomerase family(Swiss-prot: Q8FZU1).
MUTATION: ilvC is one of the 37 mutants with virulene defect, screened out from the signature- tagged miniTn5 library (PubMed: 14638795). |
| 122 |
ilvD |
G: Carbohydrate transport and metabolism |
Yes |
Protein name(s): Dihydroxy-acid dehydratase (EC 4.2.1.9) (DAD)(Swiss-prot: Q8G353).
CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(Swiss-prot: Q8G353).
COFACTOR: Binds 1 4Fe-4S cluster (Potential)(Swiss-prot: Q8G353).
PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-isoleucine from 2-oxobutanoate: step 3(Swiss-prot: Q8G353).
PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from pyruvate: step 3(Swiss-prot: Q8G353).
SIMILARITY: Belongs to the ilvD/edd family(Swiss-prot: 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 (PubMed: 15271960). |
| 123 |
ilvI |
H: Coenzyme transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis (PubMed: 14979322).
FUNCTION: Val. Leu., Isoleu. Synthesis (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 124 |
leuA |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): 2-isopropylmalate synthase (EC 2.3.3.13) (Alpha-isopropylmalate synthase) (Alpha-IPM synthetase)(Swiss-prot: Q8FZC4).
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)(Swiss-prot: Q8FZC4).
CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(Swiss-prot: Q8FZC4).
PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 1(Swiss-prot: Q8FZC4).
SUBUNIT: Homotetramer (By similarity)(Swiss-prot: Q8FZC4).
SIMILARITY: Belongs to the alpha-IPM synthetase/homocitrate synthase family. LeuA type 2 subfamily(Swiss-prot: Q8FZC4).
MUTATION: leuA is a B. suis gene identified by signature-tagged mutagenesis. It is attenuated inside THP1 macrophage cell line. |
| 125 |
leuC |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): 3-isopropylmalate dehydratase large subunit (EC 4.2.1.33) (Isopropylmalate isomerase) (Alpha-IPM isomerase) (IPMI)(Swiss-prot: Q8FYG9).
FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(Swiss-prot: Q8FYG9).
CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(Swiss-prot: Q8FYG9).
CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(Swiss-prot: Q8FYG9).
COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(Swiss-prot: Q8FYG9).
PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 2(Swiss-prot: Q8FYG9).
SUBUNIT: Heterodimer of leuC and leuD (By similarity)(Swiss-prot: Q8FYG9).
SIMILARITY: Belongs to the aconitase/IPM isomerase family. LeuC type 1 subfamily(Swiss-prot: 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 (PubMed: 12438693). |
| 126 |
livH |
E: Amino acid transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Transport (PubMed: 14979322).
FUNCTION: Branched as transport system (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction (PubMed: 14979322). |
| 127 |
lon |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
Protein name(s): ATP-dependent protease La (EC 3.4.21.53)(Swiss-prot: Q8G0I7).
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)(Swiss-prot: Q8G0I7).
CATALYTIC ACTIVITY: Hydrolysis of proteins in presence of ATP(Swiss-prot: Q8G0I7).
SUBUNIT: Homotetramer (By similarity)(Swiss-prot: Q8G0I7).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: Q8G0I7).
SIMILARITY: Belongs to the peptidase S16 family(Swiss-prot: Q8G0I7).
SIMILARITY: Contains 1 Lon domain(Swiss-prot: 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 (PubMed: 10672180).
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 (PubMed: 10878125). |
| 128 |
lpsA |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (PubMed: 14979322).
FUNCTION: putative glycosyltranferase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 129 |
lpsB |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (PubMed: 14979322).
FUNCTION: Core synthesis (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 130 |
lysA |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): diaminopimelate decarboxylase
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 (PubMed: 12438693). |
| 131 |
lysR |
K: Transcription |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (PubMed: 14979322).
FUNCTION: Transcriptional regulator (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 132 |
lysR12 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: lysR family (PubMed: 16113274).
MUTATION: Attenuated using plasmid-tagged mutagenesis method (PubMed: 16113274). |
| 133 |
lysR13 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: lysR family (PubMed: 16113274).
MUTATION: Attenuated using plasmid-tagged mutagenesis method (PubMed: 16113274). |
| 134 |
lysR18 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: lysR family (PubMed: 16113274).
MUTATION: Attenuated using plasmid-tagged mutagenesis method (PubMed: 16113274). |
| 135 |
macA |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (PubMed: 14979322).
FUNCTION: Macrolide efflux (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 136 |
malK |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Transport (PubMed: 14979322).
FUNCTION: Maltose transport (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, but not in HeLa (PubMed: 14979322). |
| 137 |
manB |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (PubMed: 14979322).
FUNCTION: O-chain biosynthesis (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 138 |
metH |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): 5-methyltetrahydrofolate--homocysteine methyltransferase
FUNCTIONAL GROUP: a.a. metabolism, Synthesis (PubMed: 14979322).
FUNCTION: Met. synthesis (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 139 |
mgps |
L: Replication, recombination and repair |
Yes |
FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation (PubMed: 14979322).
FUNCTION: RNA helicase family (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 140 |
mgtA |
N/A
|
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan (PubMed: 14979322).
FUNCTION: Peptidoglycan transglycosylase (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction, Mice, Macrophage, HeLa (PubMed: 14979322). |
| 141 |
mgtB |
P: Inorganic ion transport and metabolism |
Yes |
FUNCTIONAL GROUP: Metal acquisition (PubMed: 14979322).
FUNCTION: Mg2+ uptake (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 142 |
miaA |
J: Translation |
Yes |
Protein name(s): tRNA delta(2)-isopentenylpyrophosphate transferase (EC 2.5.1.8) (IPP transferase) (Isopentenyl-diphosphate:tRNA isopentenyltransferase) (IPTase) (IPPT)(Swiss-prot: Q8CY40).
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)(Swiss-prot: Q8CY40).
CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(Swiss-prot: Q8CY40).
SIMILARITY: Belongs to the IPP transferase family(Swiss-prot: 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 (PubMed: 12438693). |
| 143 |
mocC |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: Rhizopine/inositol catabolism (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction, Mice, but not in Macrophages, HeLa (PubMed: 14979322). |
| 144 |
mosA |
N/A
|
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: Inosamine (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 145 |
mosC |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Transport (PubMed: 14979322).
FUNCTION: Rhizopine transport (PubMed: 14979322).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (PubMed: 14979322). |
| 146 |
motB |
N: Cell motility |
Yes |
Protein name(s): flagellar motor protein
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (PubMed: 14979322).
FUNCTION: Flagellar motor (PubMed: 14979322).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (PubMed: 14979322). |
| 147 |
mtgA |
M: Cell wall/membrane biogenesis |
No |
Protein name(s): Monofunctional biosynthetic peptidoglycan transglycosylase (EC 2.4.2.-) (Monofunctional TGase)(Swiss-prot: Q8FYT4).
FUNCTION: Cell wall formation (By similarity)(Swiss-prot: Q8FYT4).
PATHWAY: Peptidoglycan synthesis; final stages(Swiss-prot: Q8FYT4).
SUBCELLULAR LOCATION: Membrane-associated (Potential)(Swiss-prot: Q8FYT4).
SIMILARITY: Belongs to the glycosyltransferase 51 family(Swiss-prot: Q8FYT4).
MUTATION: mtgA gene encodes for a monofunctional biosynthesis peptidoglycan transglycosylase (mtgA) gene that catalyzes the final stages of the peptidoglycan membrane synthesis. B abortus mtgA insertional mutants mtgA::kan demonstrated no significant growth defects in broth culture when compared to the parental strain S2308. The gene was not required for B abortus S2308 replication in RAW 264.7 macrophages. However, experimental evidence using interferon regulatory factor 1 knockout mice , a mouse strain highly susceptible to virulent Brucella, revealed that mice infected with B abortus mtgA::kan survived longer than mice infected with S2308. Together, these results suggest that B abortus mtgA plays a role during the initial phase of infection in mice (PubMed: 15519045). |
| 148 |
mutM |
L: Replication, recombination and repair |
Yes |
Protein name(s): Formamidopyrimidine-DNA glycosylase (EC 3.2.2.23) (Fapy-DNA glycosylase) (DNA-(apurinic or apyrimidinic site) lyase mutM) (EC 4.2.99.18) (AP lyase mutM)(Swiss-prot: Q8FXR6).
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)(Swiss-prot: Q8FXR6).
CATALYTIC ACTIVITY: Hydrolysis of DNA containing ring-opened N(7)-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine(Swiss-prot: 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(Swiss-prot: Q8FXR6).
COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-prot: Q8FXR6).
SUBUNIT: Monomer (By similarity)(Swiss-prot: Q8FXR6).
SIMILARITY: Belongs to the FPG family(Swiss-prot: Q8FXR6).
SIMILARITY: Contains 1 FPG-type zinc finger(Swiss-prot: Q8FXR6).
MUTATION: Attenuated in Differential fluorescence induction (PubMed: 14979322). |
| 149 |
narG |
C: Energy production and conversion |
Yes |
Protein name(s): respiratory nitrate reductase, alpha subunit
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 (PubMed: 12438693). 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 (PubMed: 12438693). |
| 150 |
ndrI |
F: Nucleotide transport and metabolism |
Yes |
FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis (PubMed: 14979322).
FUNCTION: Ribonucleotide recuctase (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction, HeLa, but not in Macrophages (PubMed: 14979322). |
| 151 |
ndvB |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: Synthesis of cyclic ( (PubMed: 14979322).
MUTATION: Attenuated in Mice, HeLa (PubMed: 14979322). |
| 152 |
nifS |
E: Amino acid transport and metabolism |
Yes |
FUNCTIONAL GROUP: Nitrogen metabolism (PubMed: 14979322).
FUNCTION: nitrogenase cofactor synthesis protein nifS (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 153 |
nikA |
E: Amino acid transport and metabolism |
Yes |
FUNCTIONAL GROUP: Metal acquisition (PubMed: 14979322).
FUNCTION: Ni2+ uptake (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages, Mice (PubMed: 14979322). |
| 154 |
nodV |
T: Signal transduction mechanisms |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Histidine kinase (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 155 |
norD |
P: Inorganic ion transport and metabolism |
Yes |
Protein name(s): norD protein
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. (PubMed: 16495577). |
| 156 |
norE |
C: Energy production and conversion |
Yes |
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: Nitric oxide reduction (PubMed: 14979322).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (PubMed: 14979322). |
| 157 |
norM |
N/A
|
Yes |
Protein name(s): Probable multidrug resistance protein norM (Multidrug-efflux transporter)(Swiss-prot: Q8G2I1).
FUNCTION: Multidrug efflux pump (By similarity)(Swiss-prot: Q8G2I1).
SUBCELLULAR LOCATION: Inner membrane; multi-pass membrane protein (By similarity)(Swiss-prot: Q8G2I1).
SIMILARITY: Belongs to the multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family(Swiss-prot: Q8G2I1).
MUTATION: A B melitensis homolog of NorM was recently identified as a potential virulence factor, as strains with mutations in its gene could not be recovered from animals infected with pools of signature tag mutants (PubMed: 12183269). |
| 158 |
nrdH |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
Protein name(s): glutaredoxin-like protein nrdH
FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis (PubMed: 14979322).
FUNCTION: Ribonucleotide recuctase (PubMed: 14979322).
MUTATION: Attenuated in HeLa, but not in Macrophages, mice (PubMed: 14979322). |
| 159 |
ntrC |
T: Signal transduction mechanisms |
Yes |
Protein name(s): nitrogen regulation protein NtrC
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 (PubMed: 10373105). |
| 160 |
ntrY |
T: Signal transduction mechanisms |
Yes |
Protein name(s): nitrogen regulation protein NtrY
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 (PubMed: 10678941). |
| 161 |
omp10 |
-: Not in COGs |
Yes |
Protein name(s): Outer membrane lipoprotein omp10 precursor (Minor outer membrane protein omp10) (10-kDa OMP)(Swiss-prot: P0A3N9).
SUBCELLULAR LOCATION: Outer membrane; lipid-anchor(Swiss-prot: P0A3N9).
MISCELLANEOUS: Elicits an immune response in B.melitensis-infected sheep but not in B.abortus-infected cattle(Swiss-prot: P0A3N9).
SIMILARITY: Belongs to the rhizobiaceae omp10 lipoprotein family(Swiss-prot: 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 (PubMed: 12228280). |
| 162 |
omp19 |
-: Not in COGs |
Yes |
Protein name(s): Outer membrane lipoprotein omp19 precursor (Minor outer membrane protein omp19) (19-kDa OMP) (18 kDa immunoreactive antigen)(Swiss-prot: P0A3P2).
SUBCELLULAR LOCATION: Outer membrane; lipid-anchor(Swiss-prot: 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(Swiss-prot: P0A3P2).
SIMILARITY: Belongs to the rhizobiaceae omp19 lipoprotein family(Swiss-prot: 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 (PubMed: 12228280). |
| 163 |
omp25 |
M: Cell wall/membrane biogenesis |
Yes |
Protein name(s): 25 kDa outer-membrane immunogenic protein precursor(Swiss-prot: Q45689).
SUBCELLULAR LOCATION: Outer membrane(Swiss-prot: Q45689).
SIMILARITY: Belongs to the omp25/ropB family(Swiss-prot: 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 (PubMed: 11447156).
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 (PubMed: 12151196).
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 (PubMed: 16077108). B abortus mutants carrying Omp25 deletions do not show enrichment of underacylated LPS (PubMed: 16077108).
Brucella spp. omp25 deletion mutants are attenuated in mice, cattle and goats, showing the involvement of Brucella spp. Omp25 in virulence (PubMed: 15374004). |
| 164 |
omp31 |
N/A
|
No |
Protein name(s): 31 kDa outer-membrane immunogenic protein precursor(Swiss-prot: P0A3U5).
FUNCTION: Major outer membrane protein associated with peptidoglycans. May function as a porin(Swiss-prot: P0A3U5).
SUBUNIT: Oligomeric(Swiss-prot: P0A3U5).
SUBCELLULAR LOCATION: Outer membrane(Swiss-prot: P0A3U5).
SIMILARITY: Belongs to the omp25/ropB family(Swiss-prot: P0A3U5).
MUTATION: Omp31 is a Brucella major outer membrane protein. Omp31 is an immunodominant antigen in the serological responses of B melitensis and B ovis infected sheep. In contrast to WT B suis or Deltaomp31 B suis, Deltaomp25 B suis induced TNF-alpha production when phagocytosed by human macrophages.
The Brucella melitensis omp31 deletion mutant ise indistinguishable from the parental Rev.1 strain by conventional bacteriological and typing tests. The expression of its major surface antigens, as determined by reactivity with specific monoclonal antibodies (MAbs), remained unaffected, ie smooth-lipopolysaccharide (S-LPS) and OMPs besides in the expression of the antigens whose respective genes were deleted. The omp31 deletion did not modify the kinetics of splenic infection nor the residual virulence of Rev.1 in the BALBc mouse model. Vaccination of BALBc mice with the deletion mutants conferred significant protective immunity against B melitensis strain H38 or B ovis strain PA challenges, to the same extent as that induced by parental Rev.1 strain. Thus, the Rev.1 omp31 deletion mutant is a promising vaccine candidate against B melitensis and B ovis infections (PubMed: 15246618). |
| 165 |
oxyR |
K: Transcription |
Yes |
Protein name(s): transcriptional regulator OxyR
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 (PubMed: 10986275). |
| 166 |
pcs |
I: Lipid transport and metabolism |
Yes |
Protein name(s): phosphatidylcholine synthase
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 (PubMed: 16882035). |
| 167 |
pepN |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): aminopeptidase N
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 (PubMed: 12933870). |
| 168 |
perA |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (PubMed: 14979322).
FUNCTION: O-chain biosynthesis (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 169 |
pgi |
G: Carbohydrate transport and metabolism |
Yes |
Protein name(s): Glucose-6-phosphate isomerase (EC 5.3.1.9) (GPI) (Phosphoglucose isomerase) (PGI) (Phosphohexose isomerase) (PHI)(Swiss-prot: Q8G2N3).
CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(Swiss-prot: Q8G2N3).
PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 2(Swiss-prot: Q8G2N3).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: Q8G2N3).
SIMILARITY: Belongs to the GPI family(Swiss-prot: 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 (PubMed: 10678941). |
| 170 |
pgm |
G: Carbohydrate transport and metabolism |
Yes |
Protein name(s): phosphoglucomutase
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 (PubMed: 10992476).
B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro (PubMed: 12525425). |
| 171 |
pheA |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): prephenate dehydratase
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 (PubMed: 15271960). |
| 172 |
pheB |
E: Amino acid transport and metabolism |
Yes |
FUNCTIONAL GROUP: Other genes (PubMed: 14979322).
FUNCTION: Dioxygenase (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 173 |
pmm |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (PubMed: 14979322).
FUNCTION: O-chain biosynthesis (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 174 |
pmtA |
I: Lipid transport and metabolism |
Yes |
Protein name(s): phospholipid N-methyltransferase
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 (PubMed: 16882035). |
| 175 |
pncA |
Q: Secondary metabolites biosynthesis, transport and catabolism |
Yes |
Protein name(s): pyrazinamidase/nicotinamidase
MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells (PubMed: 12761078). 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 (PubMed: 15135535). 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 (PubMed: 15135535). It indicates that the mutant has reduced virulence in mice. |
| 176 |
ppiD |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: Stress proteins/Chaperones (PubMed: 14979322).
FUNCTION: Rotamase D (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 177 |
pstP |
T: Signal transduction mechanisms |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (PubMed: 14979322).
FUNCTION: Phosphoenolypruvate phosphotransferase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 178 |
pth |
J: Translation |
Yes |
Protein name(s): Peptidyl-tRNA hydrolase (EC 3.1.1.29) (PTH)(Swiss-prot: P65864).
FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(Swiss-prot: P65864).
CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(Swiss-prot: P65864).
SUBUNIT: Monomer (By similarity)(Swiss-prot: P65864).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: P65864).
SIMILARITY: Belongs to the PTH family(Swiss-prot: 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 (PubMed: 15385478). |
| 179 |
purD |
F: Nucleotide transport and metabolism |
Yes |
Protein name(s): Phosphoribosylamine--glycine ligase (EC 6.3.4.13) (GARS) (Glycinamide ribonucleotide synthetase) (Phosphoribosylglycinamide synthetase)(Swiss-prot: Q8G2B1).
CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(Swiss-prot: Q8G2B1).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; N(1)-(5-phospho-D-ribosyl)glycinamide from 5-phospho-alpha-D-ribose 1-diphosphate: step 2(Swiss-prot: Q8G2B1).
PATHWAY: Context: Purine biosynthesis(Swiss-prot: Q8G2B1).
SIMILARITY: Belongs to the GARS family(Swiss-prot: Q8G2B1).
SIMILARITY: Contains 1 ATP-grasp domain(Swiss-prot: 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 (PubMed: 15271960).
Like the purE mutant, a purD::Tn10 mutant has reduced survival in murine macrophages and reduced virulence in mice (PubMed: 7642258). |
| 180 |
purE |
F: Nucleotide transport and metabolism |
Yes |
Protein name(s): Phosphoribosylaminoimidazole carboxylase catalytic subunit (EC 4.1.1.21) (AIR carboxylase) (AIRC)(Swiss-prot: Q8FYW3).
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)(Swiss-prot: Q8FYW3).
CATALYTIC ACTIVITY: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO(2)(Swiss-prot: 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(Swiss-prot: Q8FYW3).
PATHWAY: Context: Purine biosynthesis(Swiss-prot: Q8FYW3).
SUBUNIT: Homooctamer (By similarity)(Swiss-prot: Q8FYW3).
SIMILARITY: Belongs to the AIR carboxylase family(Swiss-prot: 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 (PubMed: 15271960). The purE mutant has reduced survival in murine macrophages and reduced virulence in mice (PubMed: 7642258).
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 (PubMed: 8698463). |
| 181 |
purF |
F: Nucleotide transport and metabolism |
Yes |
Protein name(s): amidophosphoribosyltransferase
MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth (PubMed: 12761078). |
| 182 |
purH |
F: Nucleotide transport and metabolism |
Yes |
Protein name(s): Bifunctional purine biosynthesis protein purH [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase (EC 2.1.2.3) (AICAR transformylase); IMP cyclohydrolase (EC 3.5.4.10) (Inosinicase) (IMP synthetase) (ATIC)](Swiss-prot: P67540).
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(Swiss-prot: P67540).
CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-prot: 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(Swiss-prot: P67540).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide: single step [final step](Swiss-prot: P67540).
PATHWAY: Context: Purine biosynthesis(Swiss-prot: P67540).
DOMAIN: The IMP cyclohydrolase activity resides in the N-terminal region (By similarity)(Swiss-prot: P67540).
SIMILARITY: Belongs to the purH family(Swiss-prot: P67540).
MUTATION: B. abortus mutant with mini-Tn5-disrupted purH displays nutritional defects in vitro (PubMed: 15271960). |
| 183 |
purK |
F: Nucleotide transport and metabolism |
No |
Protein name(s): Phosphoribosylaminoimidazole carboxylase ATPase subunit (EC 4.1.1.21) (AIR carboxylase) (AIRC)(Swiss-prot: P52559).
FUNCTION: Possesses an ATPase activity that is dependent on the presence of AIR (aminoimidazole ribonucleotide). The association of purK and purE produces an enzyme complex capable of converting AIR to CAIR efficiently under physiological condition (By similarity)(Swiss-prot: P52559).
CATALYTIC ACTIVITY: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO(2)(Swiss-prot: P52559).
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(Swiss-prot: P52559).
PATHWAY: Context: Purine biosynthesis(Swiss-prot: P52559).
SUBUNIT: Homodimer (By similarity)(Swiss-prot: P52559).
SIMILARITY: Belongs to the purK/purT family(Swiss-prot: P52559).
SIMILARITY: Contains 1 ATP-grasp domain(Swiss-prot: P52559).
CAUTION: Ref.1 sequence differs from that shown due to frameshifts in positions 22, 43, 63, 67, 140 and 150(Swiss-prot: P52559).
MUTATION: A defined B melitensis purK mutant required an elevated CO2 concentration but not supplemental purines for growth on minimal media. The purK mutant grew on minimal media only when incubated in 5% CO2 (PubMed: 7642258). |
| 184 |
purL |
F: Nucleotide transport and metabolism |
Yes |
Protein name(s): Phosphoribosylformylglycinamidine synthase II (EC 6.3.5.3) (FGAM synthase II)(Swiss-prot: Q8G183).
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(Swiss-prot: 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(Swiss-prot: Q8G183).
PATHWAY: Context: Purine biosynthesis(Swiss-prot: Q8G183).
SUBUNIT: Heterodimer of two subunits, purQ and purL(Swiss-prot: Q8G183).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: Q8G183).
SIMILARITY: Belongs to the FGAMS family(Swiss-prot: 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 (PubMed: 15271960). 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 (PubMed: 12414155). |
| 185 |
purM |
F: Nucleotide transport and metabolism |
Yes |
Protein name(s): Phosphoribosylformylglycinamidine cyclo-ligase (EC 6.3.3.1) (AIRS) (Phosphoribosyl-aminoimidazole synthetase) (AIR synthase)(Swiss-prot: Q8G1K5).
CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(Swiss-prot: 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(Swiss-prot: Q8G1K5).
PATHWAY: Context: Purine biosynthesis(Swiss-prot: Q8G1K5).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: Q8G1K5).
SIMILARITY: Belongs to the AIR synthase family(Swiss-prot: Q8G1K5).
MUTATION: B. abortus purM gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study (PubMed: 12761078). |
| 186 |
purN |
F: Nucleotide transport and metabolism |
Yes |
Protein name(s): phosphoribosylglycinamide formyltransferase
MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study (PubMed: 12761078). |
| 187 |
pyc |
C: Energy production and conversion |
Yes |
Protein name(s): pyruvate carboxylase
MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages (PubMed: 10678941). |
| 188 |
pyrB |
F: Nucleotide transport and metabolism |
Yes |
Protein name(s): Aspartate carbamoyltransferase (EC 2.1.3.2) (Aspartate transcarbamylase) (ATCase)(Swiss-prot: P65612).
CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(Swiss-prot: P65612).
PATHWAY: Nucleotide biosynthesis; UMP biosynthesis; UMP from HCO(3)(-): step 2(Swiss-prot: P65612).
PATHWAY: Context: Pyrimidine biosynthesis(Swiss-prot: P65612).
SIMILARITY: Belongs to the ATCase/OTCase family(Swiss-prot: P65612).
MUTATION: B. abortus pyrB (pyrimidines) gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study (PubMed: 12761078). |
| 189 |
pyrC |
F: Nucleotide transport and metabolism |
Yes |
FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis (PubMed: 14979322).
FUNCTION: dihydroorotase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 190 |
pyrD |
F: Nucleotide transport and metabolism |
Yes |
Protein name(s): dihydroorotate dehydrogenase
MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth (PubMed: 12761078). |
| 191 |
radA |
O: Posttranslational modification, protein turnover, chaperones |
No |
Protein name(s): DNA repair protein RadA
MUTATION: B abortus RadA complements a radA defect in E coli but could not act in place of the B abortus RecA (PubMed: 16816190). |
| 192 |
rbsC |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (PubMed: 14979322).
FUNCTION: ABC transporter (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 193 |
rbsK |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: Ribokinase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 194 |
recA |
L: Replication, recombination and repair |
Yes |
Protein name(s): Protein recA (Recombinase A)(Swiss-prot: P65976).
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)(Swiss-prot: P65976).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: P65976).
SIMILARITY: Belongs to the recA family(Swiss-prot: 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 (PubMed: 8321120).
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 (PubMed: 12414170).
|
| 195 |
rfbD |
M: Cell wall/membrane biogenesis |
Yes |
Protein name(s): O-antigen export system permease protein RfbD
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (PubMed: 14979322).
FUNCTION: O-chain biosynthesis (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages (PubMed: 14979322). |
| 196 |
rho |
K: Transcription |
No |
Protein name(s): transcription termination factor Rho
MUTATION: he number of intracellular bacteriacell increased in cells expressing positive mutant Rac and Rho (but not Cdc42) compared with control cells. The expression of dominant-negative mutant Rho proteins (RhoAN19, Rac1N17, and Cdc42N17) in transfected HeLa cells inhibited the internalization of this bacterium to different extents, supporting a role for these small GTPases in Brucella uptake (PubMed: 11579087).
In contrast to virulent Brucella, BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells (PubMed: 12414153).
The bvrS mutants do not stimulate the generation of active forms of small GTPases of the Rho family on cell contact, indicating that this two-component system is also necessary for establishing an adequate cross talk with the host cell (PubMed: 12218183). |
| 197 |
RpiR |
K: Transcription |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Transcriptional regulator (PubMed: 14979322).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (PubMed: 14979322). |
| 198 |
rplS |
J: Translation |
Yes |
Protein name(s): 50S ribosomal protein L19(Swiss-prot: P66079).
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)(Swiss-prot: P66079).
SIMILARITY: Belongs to the ribosomal protein L19P family(Swiss-prot: P66079).
MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro (PubMed: 15271960). |
| 199 |
rpoA |
K: Transcription |
Yes |
Protein name(s): DNA-directed RNA polymerase alpha chain (EC 2.7.7.6) (RNAP alpha subunit) (Transcriptase alpha chain) (RNA polymerase alpha subunit)(Swiss-prot: Q8G094).
FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(Swiss-prot: Q8G094).
CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(Swiss-prot: 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)(Swiss-prot: 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)(Swiss-prot: Q8G094).
SIMILARITY: Belongs to the RNA polymerase alpha chain family(Swiss-prot: 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 (PubMed: 14638795). |
| 200 |
rpoB |
K: Transcription |
No |
Protein name(s): DNA-directed RNA polymerase beta chain (EC 2.7.7.6) (RNAP beta subunit) (Transcriptase beta chain) (RNA polymerase beta subunit)(Swiss-prot: Q8G069).
FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(Swiss-prot: Q8G069).
CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(Swiss-prot: Q8G069).
SUBUNIT: 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)(Swiss-prot: Q8G069).
SIMILARITY: Belongs to the RNA polymerase beta chain family(Swiss-prot: Q8G069).
MUTATION: Rifampin is one of the most potent and broad-spectrum antibiotics against bacterial pathogens. Its bactericidal activity is due to its ability to bind to the beta subunit of the DNA-dependent RNA polymerase encoded by the rpoB gene. The nucleotide sequences of the rpoB gene of the Rif (r) vaccine strain Brucella abortus RB51 and of 20 Rif (r) clones derived from two Brucella melitensis isolates were determined. These sequences were then compared to those of the respective rifampin-susceptible (Rif (s)) parental strains and to the published B melitensis strain 16M. All Rif (r) strains carried one or more missense mutations mapping in two regions of the rpoB gene (PubMed: 15583262).
The presence of different mutations in the rpoB sequences of all B melitensis rough mutants did not affect the degree of virulence, since bacterial clearance was similar. However, because of the different protection provided by the strains in this study, in some cases significantly higher than that of RB51, protective properties could be affected by the rpoB genotype. Variations in the rpoB sequence, in fact, could be responsible either directly or indirectly for the induction of more potent cell-mediated responses (PubMed: 15972510). |
| 201 |
rpoN |
K: Transcription |
No |
Protein name(s): DNA-directed RNA polymerase subunit N
MUTATION: The mutants (rpoH1, rpoH2, rpoE1, rpoE2, and rpoN mutants) were characterized with regard to their sensitivity to oxidative and heat stresses. The growth curves of the rpoH1 , rpoE1 , rpoE2 , and rpoN mutants were also monitored , but no differences was observed compared to the wildtype strain. VirB8 is slightly less abundant in the rpoE1 mutant, almost absent in the rpoH2 mutant, and overproduced in the rpoN mutant compared to the wild-type strain. All mutant strains except the rpoN strain showed reduced spleen colonization after 4 weeks of infection (PubMed: 16936018). |
| 202 |
rpsA |
J: Translation |
Yes |
Protein name(s): 30S ribosomal protein S1
MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis (PubMed: 10678941). |
| 203 |
rpsL |
J: Translation |
No |
Protein name(s): 30S ribosomal protein S12(Swiss-prot: P63194).
FUNCTION: With S4 and S5 plays an important role in translational accuracy (By similarity)(Swiss-prot: P63194).
FUNCTION: Interacts with and stabilizes bases of the 16S rRNA that are involved in tRNA selection in the A site and with the mRNA backbone. Located at the interface of the 30S and 50S subunits, it traverses the body of the 30S subunit contacting proteins on the other side and probably holding the rRNA structure together. The combined cluster of proteins S8, S12 and S17 appears to hold together the shoulder and platform of the 30S subunit (By similarity)(Swiss-prot: P63194).
SUBUNIT: Part of the 30S ribosomal subunit. Contacts proteins S8 and S17. May interact with IF1 in the 30S initiation complex (By similarity)(Swiss-prot: P63194).
SIMILARITY: Belongs to the ribosomal protein S12P family(Swiss-prot: P63194).
MUTATION: Chromosomally acquired streptomycin resistance is frequently due to mutations in the gene encoding the ribosomal protein S12, rpsL. Nucleotide sequencing revealed one mutation in the rpsL gene of vaccine strain Rev. 1 compared to that of reference strain 16M leading to an amino acid Pro- to -Leu change at codon position 91 (Pro91Leu, or CCG to CTG). This mutation resulted also in the lack of a NciI restriction site in the gene (PubMed: 12057611). |
| 204 |
rsh |
N/A
|
Yes |
FUNCTION: rsh encodes a (p)ppGpp synthetase as confirmed by heterologous complementation of a relA mutant of Sinorhizobium meliloti. Expression of virB, encoding the Brucella type IV secretion system, a major virulence factor of Brucella is Rsh-dependent. It appears to be a good candidate to sense intracellular nutrient availability and to regulate virB expression (PubMed: 16803581).
MUTATION: Transposon mutants in rsh were isolated in two intracellular screens for attenuated mutants , suggesting that a functional rsh gene is essential for Brucella virulence (PubMed: 16803581).
|
| 205 |
serB |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): phosphoserine phosphatase
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 (PubMed: 12438693). |
| 206 |
sodC |
P: Inorganic ion transport and metabolism |
Yes |
Protein name(s): Superoxide dismutase [Cu-Zn] precursor (EC 1.15.1.1)(Swiss-prot: P66827).
FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(Swiss-prot: P66827).
CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(Swiss-prot: P66827).
COFACTOR: Binds 1 copper ion per subunit (By similarity)(Swiss-prot: P66827).
COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-prot: P66827).
SUBUNIT: Homodimer (By similarity)(Swiss-prot: P66827).
SUBCELLULAR LOCATION: Periplasmic (By similarity)(Swiss-prot: P66827).
SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(Swiss-prot: 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 (PubMed: 10816475)(PubMed: 11953393)(PubMed: 12933826).
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 (PubMed: 15845493). |
| 207 |
spotT |
T: Signal transduction mechanisms |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: ppGpp synthetase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 208 |
ssuB |
P: Inorganic ion transport and metabolism |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (PubMed: 14979322).
FUNCTION: Permease (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction (PubMed: 14979322). |
| 209 |
thrA |
E: Amino acid transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis (PubMed: 14979322).
FUNCTION: Lys. synthesis (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 210 |
thrC |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): threonine synthase
FUNCTIONAL GROUP: a.a. metabolism, Synthesis (PubMed: 14979322).
FUNCTION: Thre. Synthesis (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 211 |
tig |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
Protein name(s): Trigger factor (TF)(Swiss-prot: Q8G129).
FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(Swiss-prot: Q8G129).
SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(Swiss-prot: Q8G129).
SIMILARITY: Contains 1 PPIase FKBP-type domain(Swiss-prot: 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 (PubMed: 14638795). |
| 212 |
tldD |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation (PubMed: 14979322).
FUNCTION: Putative modulator of DNA gyrase (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 213 |
tpiA2 |
N/A
|
No |
Protein name(s): Triosephosphate isomerase 2 (EC 5.3.1.1) (TIM 2) (Triose-phosphate isomerase 2)(Swiss-prot: Q8FVH2).
CATALYTIC ACTIVITY: D-glyceraldehyde 3-phosphate = glycerone phosphate(Swiss-prot: Q8FVH2).
PATHWAY: Plays an important role in several metabolic pathways(Swiss-prot: Q8FVH2).
SUBUNIT: Homodimer (By similarity)(Swiss-prot: Q8FVH2).
SIMILARITY: Belongs to the triosephosphate isomerase family(Swiss-prot: Q8FVH2).
MUTATION: Addition of erythritol to VMM medium containing mannitol inhibited the growth of eryC , deoR, tpiA2 and rpiB mutants but did not impair growth of the eryA, eryD, hyp, eryE or eryF mutants. The toxic effect of erythritol on the eryC, deoR, tpiA2 and rpiB mutants suggests that a build-up of phosphorylated intermediates in the erythritol catabolic pathway is detrimental to the cell. The tpiA2 mutant was capable of growing on glycerol as a sole carbon source. The tpiA2 mutant was unable to grow on erythritol but was able to grow on glycerol (PubMed: 16804181).
|
| 214 |
trkH |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: Thioredoxin reductase (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction (PubMed: 14979322). |
| 215 |
trpB |
E: Amino acid transport and metabolism |
No |
Protein name(s): Tryptophan synthase beta chain (EC 4.2.1.20)(Swiss-prot: Q8FXY4).
FUNCTION: The beta subunit is responsible for the synthesis of L-tryptophan from indole and L-serine(Swiss-prot: Q8FXY4).
CATALYTIC ACTIVITY: L-serine + 1-(indol-3-yl)glycerol 3-phosphate = L-tryptophan + glyceraldehyde 3-phosphate(Swiss-prot: Q8FXY4).
COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-prot: Q8FXY4).
PATHWAY: Amino-acid biosynthesis; L-tryptophan biosynthesis; L-tryptophan from chorismate: step 5 [final step](Swiss-prot: Q8FXY4).
SUBUNIT: Tetramer of two alpha and two beta chains (By similarity)(Swiss-prot: Q8FXY4).
SIMILARITY: Belongs to the trpB family(Swiss-prot: Q8FXY4).
MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model, while isogenic mutants with mini-Tn5 insertions in pheA, trpB, and dagA display little or no attenuation in cultured murine macrophages or mice. These experimental findings confirm the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages (PubMed: 15271960). |
| 216 |
ugpA |
G: Carbohydrate transport and metabolism |
Yes |
Protein name(s): glycerol-3-phosphate ABC transporter, permease protein
MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice (PubMed: 14638795). |
| 217 |
ugpB |
G: Carbohydrate transport and metabolism |
Yes |
Protein name(s): glycerol-3-phosphate ABC transporter, periplasmic glycerol-3-phosphate-binding protein
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. (PubMed: 16817909). |
| 218 |
uppS |
I: Lipid transport and metabolism |
Yes |
Protein name(s): Undecaprenyl pyrophosphate synthetase (EC 2.5.1.31) (UPP synthetase) (Di-trans,poly-cis-decaprenylcistransferase) (Undecaprenyl diphosphate synthase) (UDS)(Swiss-prot: Q8G0D9).
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)(Swiss-prot: Q8G0D9).
CATALYTIC ACTIVITY: Di-trans,poly-cis-decaprenyl diphosphate + isopentenyl diphosphate = diphosphate + di-trans,poly-cis-undecaprenyl diphosphate(Swiss-prot: Q8G0D9).
COFACTOR: Magnesium (By similarity)(Swiss-prot: Q8G0D9).
SUBUNIT: Homodimer (By similarity)(Swiss-prot: Q8G0D9).
SIMILARITY: Belongs to the UPP synthetase family(Swiss-prot: 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 (PubMed: 12438693). |
| 219 |
uvrA |
L: Replication, recombination and repair |
Yes |
Protein name(s): UvrABC system protein A (UvrA protein) (Excinuclease ABC subunit A)(Swiss-prot: Q8G0I9).
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)(Swiss-prot: Q8G0I9).
SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(Swiss-prot: Q8G0I9).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: Q8G0I9).
SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(Swiss-prot: Q8G0I9).
SIMILARITY: Contains 2 ABC transporter domains(Swiss-prot: 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 (PubMed: 16816190). |
| 220 |
virB |
N/A
|
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Type IV (PubMed: 14979322).
FUNCTION: Macromolecule secrection (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 221 |
virB1 |
M: Cell wall/membrane biogenesis |
Yes |
Protein name(s): type IV secretion system protein VirB1
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 (PubMed: 15322008).
A B abortus polar virB1 mutant failed to replicate in HeLa cells, indicating that the virB operon plays a critical role in intracellular multiplication (PubMed: 10940027).
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 (PubMed: 16113325).
An infection assay with signature-tagged Brucella abortus mutants demonstrated that mutagenesis of the virB1 gene causes attenuation of virulence (PubMed: 16272371). |
| 222 |
virB10 |
U: Intracellular trafficking and secretion |
Yes |
Protein name(s): type IV secretion system protein VirB10
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 (PubMed: 10940027).
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 (PubMed: 12925673).
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 (PubMed: 10858227).
A B abortus virB10 mutant lost the ability to multiply in HeLa cells and was not recovered from the spleens of infected BALBc mice (PubMed: 11401996).
The non polar virB10 mutant was able to block the acquisition of cathepsin D, but was not able to translocate to the replication compartment (PubMed: 12414154).
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 (PubMed: 11260139). |
| 223 |
virB11 |
U: Intracellular trafficking and secretion |
Yes |
Protein name(s): type IV secretion system protein VirB11
MUTATION: The virB11 mutation experiment confirms that a complete VirB apparatus is required for their secretion (PubMed: 15312849). |
| 224 |
virB2 |
-: Not in COGs |
Yes |
Protein name(s): type IV secretion system protein VirB2
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 (PubMed: 15322008).
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 (PubMed: 16113325). |
| 225 |
virB3 |
U: Intracellular trafficking and secretion |
Yes |
Protein name(s): type IV secretion system protein VirB3.
MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells (PubMed: 12761078). |
| 226 |
virB4 |
U: Intracellular trafficking and secretion |
Yes |
Protein name(s): type IV secretion system protein VirB4
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 (PubMed: 11988518). 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 (PubMed: 15869716).
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 (PubMed: 15135535). |
| 227 |
virB5 |
-: Not in COGs |
Yes |
Protein name(s): type IV secretion system protein VirB5
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 (PubMed: 12595417).
Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion (PubMed: 12595466).
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 (PubMed: 16113325).
Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages (PubMed: 10510235). |
| 228 |
virB6 |
U: Intracellular trafficking and secretion |
Yes |
Protein name(s): type IV secretion system protein VirB6
MUTATION: B. abortus virB6 is essential for intracellular growth within HeLa cells as shown from a mutagenesis study. |
| 229 |
virB8 |
U: Intracellular trafficking and secretion |
Yes |
Protein name(s): type IV secretion system protein VirB8
MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis (PubMed: 10678941). 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 (PubMed: 12414149). |
| 230 |
virB9 |
U: Intracellular trafficking and secretion |
Yes |
Protein name(s): type IV secretion system protein VirB9
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 (PubMed: 11349069).
Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages (PubMed: 10510235).
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 (PubMed: 11437834).
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 (PubMed: 12414149). |
| 231 |
vjbR |
K: Transcription |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Transcriptional regulator (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 232 |
vsrB |
T: Signal transduction mechanisms |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Histidine kinase (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 233 |
wbdA |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (PubMed: 14979322).
FUNCTION: O-chain biosynthesis (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 234 |
wbkA |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (PubMed: 14979322).
FUNCTION: O-chain biosynthesis (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 235 |
wbkB |
-: Not in COGs |
Yes |
Protein name(s): wbkB protein
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 (PubMed: 11081580). |
| 236 |
wboA |
M: Cell wall/membrane biogenesis |
Yes |
Protein name(s): glycosyl transferase WboA
MUTATION: The wboA gene encodes the enzyme glycosyltransferas, an enzyme essential for the synthesis of O antigen. The wboA gene in RB51 is disrupted by an IS711 element and is one of many genes responsible for the rough phenotype of RB51 (PubMed: 10858205). Disruption of the wboA gene in smooth, virulent B abortus, Brucella melitensis, and Brucella suis results in rough, attenuated mutants which fail to produce the O polysaccharide (O antigen). The wboA mutants B melitensis VTRM1 and B suis VTRS1 both persist longer than 8 weeks in the spleens of BALBc mice, with splenic multiplication curves similar to that of Rev 1 (PubMed: 15099501).
The Tn5 wboA mutant B abortus RA1 is less attenuated than RB51 in mice (PubMed: 12761107). |
| 237 |
wbpL |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (PubMed: 14979322).
FUNCTION: O-chain biosynthesis (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages (PubMed: 14979322). |
| 238 |
wbpW |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (PubMed: 14979322).
FUNCTION: O-chain biosynthesis (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 239 |
wbpZ |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide (PubMed: 14979322).
FUNCTION: O-chain biosynthesis (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages (PubMed: 14979322). |
| 240 |
xerD |
L: Replication, recombination and repair |
No |
Protein name(s): Tyrosine recombinase xerD(Swiss-prot: Q7ZAN6).
FUNCTION: Site-specific tyrosine recombinase, which acts by catalyzing the cutting and rejoining of the recombining DNA molecules. The xerC-xerD complex is essential to convert dimers of the bacterial chromosome into monomers to permit their segregation at cell division. It also contributes to the segregational stability of plasmids (By similarity)(Swiss-prot: Q7ZAN6).
SUBUNIT: Forms a cyclic heterotetrameric complex composed of two molecules of xerC and two molecules of xerD (By similarity)(Swiss-prot: Q7ZAN6).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: Q7ZAN6).
SIMILARITY: Belongs to the "phage" integrase family. XerD type 1 subfamily(Swiss-prot: Q7ZAN6).
MUTATION: xerD encodes for an integraserecombinase involved in cell division. B abortus xerD::kan demonstrated no significant growth defect in broth culture when compared to the parental strain, S2308 . Also, it was not required for B abortus S2308 replication in RAW 264.7 macrophages. However, experimental evidence using interferon regulatory factor 1 knockout mice, a mouse strain highly susceptible to virulent Brucella, revealed that mice infected with B abortus xerD::kan survived longer than mice infected with S2308. Additionally, in immunocompetent BALBc mice, B abortus xerD::kan had a significantly lower level of bacterial survival when compared to S2308. Together , these results suggest that B abortus xerD plays a role during the initial phase of infection in mice (PubMed: 15519045). |
| 241 |
xfp |
G: Carbohydrate transport and metabolism |
Yes |
Protein name(s): putative phosphoketolase
FUNCTIONAL GROUP: a.a. metabolism, Degradation (PubMed: 14979322).
FUNCTION: Lys. degradation (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 242 |
xseA |
L: Replication, recombination and repair |
Yes |
Protein name(s): Probable exodeoxyribonuclease VII large subunit (EC 3.1.11.6) (Exonuclease VII large subunit)(Swiss-prot: Q8FVR1).
FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(Swiss-prot: Q8FVR1).
CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(Swiss-prot: Q8FVR1).
SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(Swiss-prot: Q8FVR1).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: Q8FVR1).
SIMILARITY: Belongs to the xseA family(Swiss-prot: Q8FVR1).
MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice (PubMed: 14638795). |
| 243 |
znuA |
P: Inorganic ion transport and metabolism |
Yes |
Protein name(s): zinc ABC transporter, periplasmic zinc-binding protein
MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells (PubMed: 12761078). 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 (PubMed: 15472468). |
| 244 |
znuC |
P: Inorganic ion transport and metabolism |
Yes |
Protein name(s): zinc ABC transporter, ATP-binding protein
FUNCTIONAL GROUP: Metal acquisition (PubMed: 14979322).
FUNCTION: Zn2+ uptake (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 245 |
zwf |
G: Carbohydrate transport and metabolism |
Yes |
Protein name(s): glucose-6-phosphate 1-dehydrogenase
MUTATION: Brucella abortus zwf mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells and macrophages (PubMed: 12761078). |
