Border Color Location
  Extracellular
  Cell membrane
  Cytoplasm
  Organelle
  Bacterial membrane or virus envelope
  Other
Backgound Color Node Shape Object Type
  Box Protein or gene
  Box Protein of gene complex
  Ellipse Pathway or action
  Box Eukaryotic cell or cell component
  Box Microorganism or its component
  Box Microbe-host cell complex

Phinet Name: Brucella suis

Phinet Information
Pathogen Name: Brucella suis
Pathogen NIAID Category: NIAID Category B
Bio-objects
Bio-object 1: Activated DnaK and other chaperones
  • Type: Protein or gene
  • Location: Organelle -- Phagosome
  • Function: Chaperone
  • Description: In Brucella suis, the DnaK expression is induced under heat-shock conditions as well as by acidic pH. Other chaperone proteins are also expressed inside the harsh environment of phagosome.(<a href="#reference5234">Kohler et al., 2002</a>)(<a href="#reference5237">Kohler et al., 2002</a>)
Bio-object 2: ahpC
  • Type: Protein or gene
Bio-object 3: ahpD
  • Type: Protein or gene
Bio-object 4: Brucella
  • Type: Microorganism or its component
  • Location: Extracellular
  • Description: Here we are focused on the pathogenesis caused by virulent smooth Brucella.(<a href="#reference5234">Kohler et al., 2002</a>)
Bio-object 5: Brucella are phagocytosed
  • Type: Pathway or action
  • Location: Cytoplasm
  • Description: Phagocytosis causes penetration of Brucella cells into macrophages(<a href="#reference5234">Kohler et al., 2002</a>)(<a href="#reference5235">Naroeni et al., 2002</a>)
Bio-object 6: Brucella associated with lipid rafts
  • Type: Complex
  • Location: Cell membrane
  • Description: Brucella is associated with macrophage lipid rafts(<a href="#reference5234">Kohler et al., 2002</a>)(<a href="#reference5235">Naroeni et al., 2002</a>)
Bio-object 7: Brucella Replicating
  • Type: Pathway or action
  • Location: Organelle -- Phagosome
  • Description: Brucella rapidly replicate inside the replicative phagosomes.(<a href="#reference5234">Kohler et al., 2002</a>)
Bio-object 8: Brucella virulent factors synthesized inside replicative phagosomes
  • Type: Protein or gene
  • Location: Organelle -- Phagosome
  • Description: Brucella virulent factors can be synthesized inside phagosomes.(<a href="#reference5234">Kohler et al., 2002</a>)
Bio-object 9: Brucella-containing vacuole
  • Type: Microbe-host cell complex
  • Location: Other
  • Description: The brucellae reside in an acified compartment that fuses with components of the early endosomal pathway immediately after entry into the macrophages.(<a href="#reference5238">Kohler et al., 2002</a>)
Bio-object 10: bvrR
  • Type: Protein or gene
Bio-object 11: bvrS
  • Type: Protein or gene
Bio-object 12: clpA
  • Type: Protein or gene
Bio-object 13: clpB
  • Type: Protein or gene
Bio-object 14: clpP
  • Type: Protein or gene
Bio-object 15: clpX
  • Type: Protein or gene
Bio-object 16: ctrA
  • Type: Protein or gene
Bio-object 17: dnaJ
  • Type: Protein or gene
Bio-object 18: dnaK
  • Type: Protein or gene
Bio-object 19: Early endosomes
  • Type: Eukaryotic cell or cell component
  • Location: Other
  • Description: The brucellae reside in an acified compartment that fuses with components of the early endosomal pathway immediately after entry into the macrophages.(<a href="#reference5238">Kohler et al., 2002</a>)
Bio-object 20: Early Phagosome
  • Type: Eukaryotic cell or cell component
  • Location: Organelle -- Phagosome
  • Description: The acidified Brucella-containing phagosome has pH 4-4.5.(<a href="#reference5234">Kohler et al., 2002</a>)(<a href="#reference5236">Porte et al., 1999</a>)(<a href="#reference5238">Kohler et al., 2002</a>)
Bio-object 21: Endoplasmic reticulum
  • Type: Eukaryotic cell or cell component
  • Location: Organelle -- ER
  • Description: The ER is involved in the formation of replicative phagosomes.(<a href="#reference5238">Kohler et al., 2002</a>)
Bio-object 22: entB
  • Type: Protein or gene
Bio-object 23: entE
  • Type: Protein or gene
Bio-object 24: ftsE
  • Type: Protein or gene
Bio-object 25: ftsK
  • Type: Protein or gene
Bio-object 26: ftsZ
  • Type: Protein or gene
Bio-object 27: fur
  • Type: Protein or gene
Bio-object 28: groEL
  • Type: Protein or gene
Bio-object 29: grpE
  • Type: Protein or gene
Bio-object 30: hdeA
  • Type: Protein or gene
Bio-object 31: hemB
  • Type: Protein or gene
Bio-object 32: hemE
  • Type: Protein or gene
Bio-object 33: hfq
  • Type: Protein or gene
Bio-object 34: Less than 10% Brucella survived in early phagosome
  • Type: Pathway or action
  • Location: Organelle -- Phagosome
  • Description: More than 90% of Brucella are killed during the early infection stage.(<a href="#reference5234">Kohler et al., 2002</a>)(<a href="#reference5236">Porte et al., 1999</a>)
Bio-object 35: Lipid rafts on macrophages
  • Type: Eukaryotic cell or cell component
  • Location: Cell membrane
  • Description: Cholesterol-rich domains (such as cholesterol and ganglioside GM1, two components of lipid rafts) are necessary for Brucella penetration.(<a href="#reference5234">Kohler et al., 2002</a>)
Bio-object 36: Macrophage cell membrane
  • Type: Eukaryotic cell or cell component
  • Location: Cell membrane
  • Description: Macrophage cell membrane is used during phagocytosis of Brucella by macrophages. The cell membrane contains the lipid rafts.(<a href="#reference5234">Kohler et al., 2002</a>)
Bio-object 37: mdh
  • Type: Protein or gene
Bio-object 38: minC
  • Type: Protein or gene
Bio-object 39: ntrB
  • Type: Protein or gene
Bio-object 40: ntrC
  • Type: Protein or gene
Bio-object 41: nusA
  • Type: Protein or gene
Bio-object 42: omp25
  • Type: Protein or gene
Bio-object 43: omp31
  • Type: Protein or gene
Bio-object 44: Proton
  • Type: Other -- ion
  • Location: Cytoplasm
  • Description: Inside the cell, a proton pump (probably of cellular origin) rapidly acidifies the phagosome resulting in a stress for the bacteria and also in a signal that triggers virulence genes activation.(<a href="#reference5234">Kohler et al., 2002</a>)(<a href="#reference5236">Porte et al., 1999</a>)
Bio-object 45: Replicative phagosomes
  • Type: Eukaryotic cell or cell component
  • Location: Organelle -- Phagosome
  • Description: Replicative phagosomes (or called brucellosome) are the intracellular niche for Brucella growth. Lysosomes do not fuse with the Brucella phagosome, and the normal trafficking of the cell is not affected during infection.(<a href="#reference5234">Kohler et al., 2002</a>)
Bio-object 46: rpoB
  • Type: Protein or gene
Bio-object 47: rpoD
  • Type: Protein or gene
Bio-object 48: sodC
  • Type: Protein or gene
Bio-object 49: Stress (acidic pH, depleted nutrient, limited oxygen)
  • Type: Pathway or action
  • Location: Organelle -- Phagosome
  • Description: The stress (nutrient depletion, acidification, hypoxia) inside phagosomes provide Brucella with a harsh environment.(<a href="#reference5234">Kohler et al., 2002</a>)
Bio-object 50: thi5
  • Type: Protein or gene
Bio-object 51: thiE
  • Type: Protein or gene
Bio-object 52: virB1
  • Type: Protein or gene
Bio-object 53: virB10
  • Type: Protein or gene
Bio-object 54: virB11
  • Type: Protein or gene
Bio-object 55: virB2
  • Type: Protein or gene
Bio-object 56: virB3
  • Type: Protein or gene
Bio-object 57: virB4
  • Type: Protein or gene
Bio-object 58: virB5
  • Type: Protein or gene
Bio-object 59: virB6
  • Type: Protein or gene
Bio-object 60: virB7
  • Type: Protein or gene
Bio-object 61: virB8
  • Type: Protein or gene
Bio-object 62: virB9
  • Type: Protein or gene
Bio-object 63: xerC
  • Type: Protein or gene
Bio-object 64: xerD
  • Type: Protein or gene
Interactions
Interaction 1: Interaction1
  • Type: Brucella associated with
  • Input Objects: Brucella, Lipid rafts on macrophages
  • Output Objects: Brucella associated with lipid rafts
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: lipid rafts on the surface of macrophages promotes the phagocytosis of Brucella cells into macrophages. Brucella avoids to induce an oxidatuve burst when it encounters its host cell(<a href="#reference5234">Kohler et al., 2002</a>)(<a href="#reference5235">Naroeni et al., 2002</a>)
Interaction 2: Interaction2
  • Type: phagocytosis
  • Input Objects: Brucella associated with lipid rafts, Macrophage cell membrane
  • Output Objects: Brucella-containing vacuole
  • GO Evidence Code: Inferred from Direct Assay
  • Description: Macrophages phagocytose Brucella and Brucella stay in membran-bound vacuole.rly endosomes.(<a href="#reference5234">Kohler et al., 2002</a>)(<a href="#reference5235">Naroeni et al., 2002</a>)(<a href="#reference5238">Kohler et al., 2002</a>)
Interaction 3: Interaction4
  • Type: Acidified early phagosome
  • Cofactors: Proton
  • Input Objects: Brucella-containing vacuole, Early endosomes
  • Output Objects: Early Phagosome
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: Inside the cell, a proton pump (probably of cellular origin) rapidly acidifies the phagosome(<a href="#reference5234">Kohler et al., 2002</a>)(<a href="#reference5236">Porte et al., 1999</a>)
Interaction 4: Interaction5
  • Input Objects: Early Phagosome
  • Output Objects: Less than 10% Brucella survived in early phagosome
  • GO Evidence Code: Inferred from Direct Assay
  • Description: about 90% Brucella are killed in acidified phagosome at the early stage of infection. Only less than 10% Brucella survive.(<a href="#reference5234">Kohler et al., 2002</a>)(<a href="#reference5236">Porte et al., 1999</a>)
Interaction 5: Interaction6
  • Type: Replicative phagosomes fo
  • Input Objects: Less than 10% Brucella survived in early phagosome, Endoplasmic reticulum
  • Output Objects: Replicative phagosomes
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: The acidified Brucella phagosome is prevented from fusion with lysosome. Lipid rafts on the phagosome are involved in the isolation of the phagosome from classical traffic. These replicative phagosomes arise through continual interactions between the Brucella-containing vacuole and the endoplasmic reticulum of the host macrophages.(<a href="#reference5234">Kohler et al., 2002</a>)(<a href="#reference5235">Naroeni et al., 2002</a>)(<a href="#reference5238">Kohler et al., 2002</a>)
Interaction 6: Interaction7
Interaction 7: Interaction8
Interaction 8: Interaction9
Interaction 9: ahpC_ahpD
  • Input Objects: ahpC, ahpD
  • GO Evidence Code: Traceable Author Statement
  • Description: B abortus ahpC is cotranscribed with Brucella ahpD. The product of ahpD is a thioredoxin-like protein that transfers reducing equivalents from the alpha-ketoglutarate dehydrogenase complex of the tricarboxylic acid cycle to AhpC, restoring the capacity of the oxidized form of this enzyme to serve as a peroxidase (<a href="#reference5709">Roop et al., 2003</a>).
Interaction 10: omp25_bvrR
  • Input Objects: omp25, bvrR
  • GO Evidence Code: Inferred from Direct Assay
  • Description: Two major sets of proteins, Omp3a (formerly Omp25) and Omp3b, related to B melitensis Omp31 (absent in B abortus), to RopB of R leguminosarum, and to AopB of A tumefaciens, were identified as regulated by the BvrR and BvrS two-component system (<a href="#reference5710">Guzman-Verri et al., 2002</a>).
Interaction 11: bvrR_bvrS
  • Input Objects: bvrR, bvrS
  • GO Evidence Code: Inferred from Direct Assay
  • Description: Brucella BvrR and BvrS two-component regulatory system is homologous to the ChvI ChvG systems of Sinorhizobium meliloti and Agrobacterium tumefaciens necessary for endosymbiosis and pathogenicity in plants. BvrR (regulator) and BvrS (sensor) controls cell invasion and intracellular survival (<a href="#reference5710">Guzman-Verri et al., 2002</a>).
Interaction 12: omp25_bvrS
  • Input Objects: omp25, bvrS
  • GO Evidence Code: Inferred from Direct Assay
  • Description: Two major sets of proteins, Omp3a (formerly Omp25) and Omp3b, related to B melitensis Omp31 (absent in B abortus), to RopB of R leguminosarum, and to AopB of A tumefaciens, were identified as regulated by the BvrR and BvrS two-component system (<a href="#reference5710">Guzman-Verri et al., 2002</a>).
Interaction 13: clpA_clpB
  • Input Objects: clpA, clpB
  • GO Evidence Code: Inferred from Mutant Phenotype
  • Description: The single-gene null mutants clpB and clpA were not more sensitive to H2O2 than the wild type, but a clpAB double mutant showed increased sensitivity. Both Clp ATPases probably participated in the oxidative stress response and could substitute for each other (<a href="#reference5711">Ekaza et al., 2001</a>). ClpA is part of the two-component protease ClpAP, and it binds protein substrates and presents them to the protease ClpP for degradation. ClpB participates in suppression and reversion of protein aggregation (<a href="#reference5711">Ekaza et al., 2001</a>).
Interaction 14: dnaK_clpB
  • Input Objects: dnaK, clpB
  • GO Evidence Code: Inferred from Direct Assay
  • Description: ClpB interacts with DnaK, DnaJ, and GrpE in suppressing and reversing protein aggregation by the formation of a bichaperone system in vitro (<a href="#reference5711">Ekaza et al., 2001</a>).
Interaction 15: grpE_clpB
  • Input Objects: grpE, clpB
  • GO Evidence Code: Inferred from Direct Assay
  • Description: ClpB interacts with DnaK, DnaJ, and GrpE in suppressing and reversing protein aggregation by the formation of a bichaperone system in vitro (<a href="#reference5711">Ekaza et al., 2001</a>).
Interaction 16: clpA_clpP
  • Input Objects: clpA, clpP
  • GO Evidence Code: Inferred from Direct Assay
  • Description: ClpA and ClpX are regulatory ATPases forming a complex with the unrelated, ATP-dependent, proteolytic component ClpP. As an essential component of the protease ClpAP complex, ClpA regulates the other major protease ClpP. In a heterologous complementation system using ClpA from B suis and ClpP from E coli, the reduction in growth inhibition caused by canavanine was due to an intimate interaction between both components. ClpA in brucellae most likely has, as in E coli, the role of binding substrates and presenting them to ClpP for degradation. The region of ClpA that interacts with ClpP has not been determined yet (<a href="#reference5712">Ekaza et al., 2000</a>).
Interaction 17: clpA_clpX
  • Input Objects: clpA, clpX
  • GO Evidence Code: Inferred from Direct Assay
  • Description: ClpA and ClpX are regulatory ATPases forming a complex with the unrelated, ATP-dependent, proteolytic component ClpP, which then removes denatured proteins by degradation. ClpX plays an essential role in B suis and its gene can not be inactivated (<a href="#reference5712">Ekaza et al., 2000</a>). ORFs for stress-induced proteins such as ClpA, ClpB, ClpP, and ClpX are located on chromosome I (<a href="#reference5713">DelVecchio et al., 2002</a>).
Interaction 18: clpP_clpX
  • Input Objects: clpP, clpX
  • GO Evidence Code: Inferred from Direct Assay
  • Description: ClpA and ClpX are regulatory ATPases forming a complex with the unrelated, ATP-dependent, proteolytic component ClpP, which then removes denatured proteins by degradation. ClpX plays an essential role in B suis and its gene can not be inactivated (<a href="#reference5712">Ekaza et al., 2000</a>). ORFs for stress-induced proteins such as ClpA, ClpB, ClpP, and ClpX are located on chromosome I (<a href="#reference5713">DelVecchio et al., 2002</a>).
Interaction 19: ftsK_ctrA
  • Input Objects: ftsK, ctrA
  • Description: CtrA binds to two ftsK genes (septation and chromosome dimer resolution) (<a href="#reference5714">Letesson et al., 2002</a>).
Interaction 20: hfq_ctrA
  • Input Objects: hfq, ctrA
  • GO Evidence Code: Traceable Author Statement
  • Description: The Brucella hfq contains a putative CtrA binding sequence overlapping the 10 region of its promoter and therefore may be under the negative control of this transcriptional regulator (<a href="#reference5715">Robertson et al., 2000</a>). hfq may be negatively regulated by CtrA (<a href="#reference5716">Boschiroli et al., 2001</a>).
Interaction 21: minC_ctrA
  • Input Objects: minC, ctrA
  • GO Evidence Code: Inferred from Direct Assay
  • Description: Footprinting experiments support that, in B abortus, CtrA might directly regulate the expression of the rpoD, pleC, minC and ftsE homologues (<a href="#reference5717">Bellefontaine et al., 2002</a>).
Interaction 22: rpoD_ctrA
  • Input Objects: rpoD, ctrA
  • GO Evidence Code: Inferred from Direct Assay
  • Description: Footprinting experiments support that, in B abortus, CtrA might directly regulate the expression of the rpoD, pleC, minC and ftsE homologues (<a href="#reference5717">Bellefontaine et al., 2002</a>).
Interaction 23: clpB_dnaJ
  • Input Objects: clpB, dnaJ
  • GO Evidence Code: Inferred from Direct Assay
  • Description: ClpB interacts with DnaK, DnaJ, and GrpE in suppressing and reversing protein aggregation by the formation of a bichaperone system in vitro (<a href="#reference5711">Ekaza et al., 2001</a>).
Interaction 24: groEL_dnaK
  • Input Objects: groEL, dnaK
  • GO Evidence Code: Inferred from Direct Assay
  • Description: The interaction between GroEL (HSP60) and DnaK (HSP70) plays a critical role in the heat shock response. Overproduction of GroEL decreased the expression of DnaK and that decreased expression of GroEL activated the expression of DnaK (<a href="#reference5718">Zhang et al., 1998</a>). In intracellular brucellae, which encounter stressful conditions such as acidic pH and possibly oxidative stress due to the presence of oxygen radicals, the known stress proteins GroEL and DnaK are induced during infection, and DnaK is essential for multiplication of B suis in macrophage-like cells (<a href="#reference5711">Ekaza et al., 2001</a>).
Interaction 25: entE_entB
  • Input Objects: entE, entB
  • GO Evidence Code: Inferred from Sequence or Structural Similarity
  • Description: The product of this gene (EntF) together with EntB and EntE constitute a multienzyme complex responsible for the biosynthesis of the catecholic siderophore enterobactin in E coli (Gehring et al, 1998) (<a href="#reference5719">Gonzalez et al., 2002</a>).
Interaction 26: ctrA_ftsE
  • Input Objects: ctrA, ftsE
  • GO Evidence Code: Inferred from Direct Assay
  • Description: Footprinting experiments indicate that, in B abortus, CtrA directly regulates the expression of the rpoD, pleC, minC and ftsE homologues (<a href="#reference5717">Bellefontaine et al., 2002</a>).
Interaction 27: dnaK_ftsZ
  • Input Objects: dnaK, ftsZ
  • GO Evidence Code: Inferred from Sequence or Structural Similarity
  • Description: Defective septation was suggested to be due to interaction between DnaK protein and proteins involved in cell division, like the FtsZ protein as shown in E. coli (Blum et aL, 1992) (<a href="#reference5720">Cloeckaert et al., 1996</a>).
Interaction 28: omp31_fur
  • Input Objects: omp31, fur
  • GO Evidence Code: Traceable Author Statement
  • Description: hbpA, pap31 and omp31 may be regulated by Fur in response to fluctuating cellular iron levels (<a href="#reference5721">Carroll et al., 2000</a>).
Interaction 29: hfq_hdeA
  • Input Objects: hfq, hdeA
  • GO Evidence Code: Inferred from Mutant Phenotype
  • Description: hdeA encodes a periplasmic low pH-dependent chaperone. This Brucella gene requires hfq-encoded HF-I for optimal expression during stationary phase (<a href="#reference5709">Roop et al., 2003</a>).
Interaction 30: hfq_hemB
  • Input Objects: hfq, hemB
  • GO Evidence Code: Inferred from Mutant Phenotype
  • Description: hemB encodes delta-aminolevulinic acid dehydratase. This Brucella gene requires hfq-encoded HF-I for optimal expression during stationary phase (<a href="#reference5709">Roop et al., 2003</a>).
Interaction 31: ctrA_hemE
  • Input Objects: ctrA, hemE
  • GO Evidence Code: Inferred from Sequence or Structural Similarity
  • Description: CtrA represses DNA replication initiation through the regulation of hemE gene whose promoter overlaps the C crescentus chromosomal origin of replication (Ori) (<a href="#reference5714">Letesson et al., 2002</a>).
Interaction 32: ahpC_hfq
  • Input Objects: ahpC, hfq
  • GO Evidence Code: Inferred from Mutant Phenotype
  • Description: Reduced expression of ahpC upon entry into stationary phase may prevent the B abortus hfq mutant Hfq3 from resisting killing by host macrophages with the same vigor as the parental 2308 strain.
Interaction 33: sodC_hfq
  • Input Objects: sodC, hfq
  • GO Evidence Code: Inferred from Direct Assay
  • Description: In E. coli and S. enterica serovar Typhimurium, RpoS, and consequently Hfq, are responsible for increased expression of sodC during stationary phase. Bacterial sodC genes are typically regulated in a growth-phase-dependent manner, and their expression is usually maximal during stationary phase. Hfq is an RNA binding protein that facilitates efficient translation of the rpoS transcript coincident with entry into stationary phase (<a href="#reference5722">Gee et al., 2005</a>). A 2-D gel analysis of lysates from B abortus 2308 and Hfq3 revealed greatly reduced sodC expression in the B abortus hfq mutant compared with the parent strain during stationary phase (<a href="#reference5709">Roop et al., 2003</a>). It is noted that greater than 40 B abortus 2308 genes require Hfq for their efficient expression during stationary phase, and experimental analysis of other Hfq regulated genes has determined that inefficient sodC expression is not the sole basis for the attenuation displayed by the B abortus hfq mutant in experimentally infected mice (<a href="#reference5722">Gee et al., 2005</a>).
Interaction 34: ahpC_mdh
  • Input Objects: ahpC, mdh
  • GO Evidence Code: Inferred from Mutant Phenotype
  • Description: Similar to the B abortus sodC, reduced expression of ahpC upon entry into stationary phase may prevent the B abortus hfq mutant Hfq3 from resisting killing by host macrophages with the same vigor as the parental 2308 strain (<a href="#reference5709">Roop et al., 2003</a>).
Interaction 35: ntrB_ntrC
  • Input Objects: ntrB, ntrC
  • GO Evidence Code: Inferred from Direct Assay
  • Description: Growth of many bacteria under nitrogen-limiting conditions results in a co-ordinated response that induces the synthesis of proteins that transport and degrade nitrogenous compounds and of glutamine synthetase (GlnA), which assimilates ammonia. This is referred to as the ntr (nitrogen regulated) response, and is the two-component regulatory system NtrBC. In Salmonella typhimurium, the glnA, ntrB and ntrC genes form an operon and single mutations in glnA, ntrB, ntrC or the gene encoding a strain with a (glnA-ntrC) operon deletion was attenuated in mice. NtrC is the a response regulator. The putative B suis ntrC gene was fully sequenced and an adjacent gene coding for the sensor protein NtrB was also identified upstream of the ntrC gene, as is the case in S typhimurium (<a href="#reference5723">Dorrell et al., 1999</a>).
Interaction 36: nusA_rpoB
  • Input Objects: nusA, rpoB
  • GO Evidence Code: Inferred from Sequence or Structural Similarity
  • Description: Rifampicin resistant (Rifr mutations) map in the rpoB gene encoding the beta subunit of Escherichia coli RNA polymerase. Rifr mutations affect both lambda N-mediated antitermination and the cellular antitermination system involved in synthesis of stable RNA. NusA is involved in antitermination and termination. It was found that Rifr mutations can either enhance or suppress the phenotypes of defective nusA alleles. Most Rifr mutations alter the temperature range over which the nusA1 allele supports lambda N-mediated antitermination. In addition, a number of Rifr alleles restore termination to the nusA10(Cs) and the nusA11(Ts) mutants defective in this process. It was suggested that the region of the rpoB gene defined by the Rifr mutations is involved in the antitermination process and affects the activity of the NusA protein directly or indirectly (<a href="#reference5724">Jin et al., 1988</a>). No report has been shown in Brucella.
Interaction 37: hfq_thi5
  • Input Objects: hfq, thi5
  • GO Evidence Code: Inferred from Mutant Phenotype
  • Description: thi5 encodes ABC transporter substrate binding protein. This Brucella gene requires hfq-encoded HF-I for optimal expression during stationary phase(<a href="#reference5709">Roop et al., 2003</a>).
Interaction 38: hfq_thiE
  • Input Objects: hfq, thiE
  • GO Evidence Code: Inferred from Mutant Phenotype
  • Description: thiE encodes thiamin-phosphate pyrophosphorylase. This Brucella gene requires hfq-encoded HF-I for optimal expression during stationary phase (<a href="#reference5709">Roop et al., 2003</a>).
Interaction 39: bvrR_virB1
  • Input Objects: bvrR, virB1
  • GO Evidence Code: Inferred from Direct Assay
  • Description: Secretion of the N-terminal fragment of BvrR fused to CAT was diminished in virB1 and virB10 mutants (<a href="#reference5725">Marchesini et al., 2004</a>).
Interaction 40: virB11_virB1
  • Input Objects: virB11, virB1
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: Based on results obtained with the yeast two-hybrid system, VirB1 may interact with several VirB proteins, such as VirB4, VirB8, VirB9, VirB10, and VirB11 (<a href="#reference5726">Hoppner et al., 2004</a>). Analysis of protein- protein interactions by affinity precipitation revealed that VirB1 bound to VirB9 and VirB11 (<a href="#reference5727">Hoppner et al., 2005</a>).
Interaction 41: virB4_virB1
  • Input Objects: virB4, virB1
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: VirB1 is a lytic transglycosylase required for T4SS early assembly. VirB2 and VirB5 are pilus components. Based on results obtained with the yeast two-hybrid system, VirB1 may interact with several VirB proteins, such as VirB4, VirB8, VirB9, VirB10, and VirB11 (<a href="#reference5726">Hoppner et al., 2004</a>).
Interaction 42: virB5_virB1
  • Input Objects: virB5, virB1
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: The expression of virB5 was reduced by polar insertions in virB1 and virB2 (<a href="#reference5728">Sun et al., 2005</a>).
Interaction 43: virB8_virB1
  • Input Objects: virB8, virB1
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: VirB8 can interact with many other T4SS proteins including VirB10, VirB9, VirB1, VirB4, and VirB11, as well as with itself (<a href="#reference5729">Terradot et al., 2005</a>).
Interaction 44: virB9_virB1
  • Input Objects: virB9, virB1
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: Based on results obtained with the yeast two-hybrid system, VirB1 may interact with several VirB proteins, such as VirB4, VirB8, VirB9, VirB10, and VirB11 (<a href="#reference5726">Hoppner et al., 2004</a>).
Interaction 45: bvrR_virB10
  • Input Objects: bvrR, virB10
  • GO Evidence Code: Inferred from Direct Assay
  • Description: Secretion of the N-terminal fragment of BvrR fused to CAT was diminished in virB1 and virB10 mutants (<a href="#reference5725">Marchesini et al., 2004</a>).
Interaction 46: virB1_virB10
  • Input Objects: virB1, virB10
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: Based on results obtained with the yeast two-hybrid system, VirB1 may interact with several VirB proteins, such as VirB4, VirB8, VirB9, VirB10, and VirB11 (<a href="#reference5726">Hoppner et al., 2004</a>). A role of VirB1 in Type 4 secretion system (T4SS) assembly via interactions with other proteins was also supported by its impact on the localization of VirB10 in the cell (<a href="#reference5726">Hoppner et al., 2004</a>). Mutation of virB1 abolishes expression of both virB7 and virB10 (<a href="#reference5728">Sun et al., 2005</a>).
Interaction 47: virB11_virB10
  • Input Objects: virB11, virB10
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: VirB10 interacts with VirB8, VirB9, VirB4, VirB1, and VirB11, as well as itself (<a href="#reference5729">Terradot et al., 2005</a>).
Interaction 48: virB4_virB10
  • Input Objects: virB4, virB10
  • Description: VirB10 interacts with VirB8, VirB9, VirB4, VirB1, and VirB11, as well as itself.
Interaction 49: virB5_virB10
  • Input Objects: virB5, virB10
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: Purified B suis VirB5 interacts with VirB8 and VirB10, and these interactions are likely required for binding to VirB2, followed by pilus assembly (<a href="#reference5730">Carle et al., 2006</a>).
Interaction 50: virB6_virB10
  • Input Objects: virB6, virB10
  • GO Evidence Code: Inferred from Direct Assay
  • Description: VirB6 has multiple transmembrane helices and forms an inner membrane complex with VirB8 and VirB10 (<a href="#reference5729">Terradot et al., 2005</a>).
Interaction 51: virB7_virB10
  • Input Objects: virB7, virB10
  • GO Evidence Code: Inferred from Direct Assay
  • Description: Biochemical experiments suggested that VirB7, VirB8, VirB9, and VirB10, which are mostly exposed to the periplasm but anchored to the membranes, constitute the core complex that makes up the central transmembrane channel and is required for the stabilization of many other membrane-bound VirB proteins (<a href="#reference5726">Hoppner et al., 2004</a>).
Interaction 52: virB8_virB10
  • Input Objects: virB8, virB10
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: VirB8 can interact with many other T4SS proteins including VirB10, VirB9, VirB1, VirB4, and VirB11, as well as with itself (<a href="#reference5729">Terradot et al., 2005</a>). VirB6 has multiple transmembrane helices and forms an inner membrane complex with VirB8 and VirB10 (<a href="#reference5729">Terradot et al., 2005</a>).
Interaction 53: virB9_virB10
  • Input Objects: virB9, virB10
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: VirB10 interacts with VirB8, VirB9, VirB4, VirB1, and VirB11, as well as itself (<a href="#reference5729">Terradot et al., 2005</a>).
Interaction 54: virB5_virB2
  • Input Objects: virB5, virB2
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: Purified B suis VirB5 interacts with VirB8 and VirB10, and these interactions are likely required for binding to VirB2, followed by pilus assembly. VirB5 undergoes different interactions in the presence and in the absence of VirB2. Incorrectly processed VirB2 may bind to VirB5 in nonproductive complexes and thereby negatively impact T4SS assembly (<a href="#reference5730">Carle et al., 2006</a>).
Interaction 55: virB4_virB3
  • Input Objects: virB4, virB3
  • GO Evidence Code: Inferred from Sequence or Structural Similarity
  • Description: The product of the virB4 gene of Agrobacterium tumefaciens promotes accumulation of VirB3 protein (<a href="#reference5731">Jones et al., 1994</a>).
Interaction 56: virB11_virB4
  • Input Objects: virB11, virB4
  • GO Evidence Code: Inferred from Direct Assay
  • Description: VirB11 and VirB4 are two highly conserved inner-membrane-bound NTPases and are involved in early substrate transfer reactions (<a href="#reference5732">de et al., 2005</a>).
Interaction 57: virB3_virB6
  • Input Objects: virB3, virB6
  • GO Evidence Code: Inferred from Sequence or Structural Similarity
  • Description: VirB6 is required for stabilization of VirB5 and VirB3 and formation of VirB7 homodimers in Agrobacterium tumefaciens (<a href="#reference5733">Hapfelmeier et al., 2000</a>).
Interaction 58: virB5_virB6
  • Input Objects: virB5, virB6
  • GO Evidence Code: Inferred from Sequence or Structural Similarity
  • Description: VirB6 is required for stabilization of VirB5 and VirB3 and formation of VirB7 homodimers in Agrobacterium tumefaciens (<a href="#reference5733">Hapfelmeier et al., 2000</a>).
Interaction 59: virB8_virB6
  • Input Objects: virB8, virB6
  • GO Evidence Code: Inferred from Direct Assay
  • Description: VirB8 and VirB6 are channel proteins (<a href="#reference5734">DelVecchio et al., 2002</a>). VirB6 has multiple transmembrane helices and forms an inner membrane complex with VirB8 and VirB10 (<a href="#reference5729">Terradot et al., 2005</a>).
Interaction 60: virB9_virB6
  • Input Objects: virB9, virB6
  • GO Evidence Code: Inferred from Sequence or Structural Similarity
  • Description: VirB9 and VirB6 are both channel proteins (<a href="#reference5734">DelVecchio et al., 2002</a>). Agrobacterium tumefaciens VirB6 protein participates in formation of VirB7 and VirB9 complexes required for type IV secretion (<a href="#reference5726">Hoppner et al., 2004</a>).
Interaction 61: virB1_virB7
  • Input Objects: virB1, virB7
  • GO Evidence Code: Inferred from Mutant Phenotype
  • Description: Mutation of virB1 abolishes expression of both virB7 and virB10 (<a href="#reference5728">Sun et al., 2005</a>).
Interaction 62: virB6_virB7
  • Input Objects: virB6, virB7
  • GO Evidence Code: Inferred from Sequence or Structural Similarity
  • Description: Agrobacterium tumefaciens VirB6 protein participates in formation of VirB7 and VirB9 complexes required for type IV secretion (<a href="#reference5735">Jakubowski et al., 2003</a>).
Interaction 63: virB8_virB7
  • Input Objects: virB8, virB7
  • GO Evidence Code: Inferred from Direct Assay
  • Description: Biochemical experiments suggested that VirB7, VirB8, VirB9, and VirB10, which are mostly exposed to the periplasm but anchored to the membranes, constitute the core complex that makes up the central transmembrane channel and is required for the stabilization of many other membrane-bound VirB proteins (<a href="#reference5726">Hoppner et al., 2004</a>).
Interaction 64: virB9_virB7
  • Input Objects: virB9, virB7
  • GO Evidence Code: Inferred from Sequence or Structural Similarity
  • Description: Agrobacterium tumefaciens VirB6 protein participates in formation of VirB7 and VirB9 complexes required for type IV secretion (<a href="#reference5726">Hoppner et al., 2004</a>). VirB9 and the lipoprotein VirB7 form an outer membrane complex (<a href="#reference5729">Terradot et al., 2005</a>).
Interaction 65: virB11_virB8
  • Input Objects: virB11, virB8
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: VirB8 can interact with many other T4SS proteins including VirB10, VirB9, VirB1, VirB4, and VirB11, as well as with itself (<a href="#reference5729">Terradot et al., 2005</a>).
Interaction 66: virB2_virB8
  • Input Objects: virB2, virB8
  • GO Evidence Code: Traceable Author Statement
  • Description: Purified B suis VirB5, which is similar to minor T -pilus components of other T4SSs, interacts with VirB8 and VirB10, and these interactions are likely required for binding to VirB2, followed by pilus assembly (<a href="#reference5730">Carle et al., 2006</a>).
Interaction 67: virB4_virB8
  • Input Objects: virB4, virB8
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: VirB8 can interact with many other T4SS proteins including VirB10, VirB9, VirB1, VirB4, and VirB11, as well as with itself (<a href="#reference5729">Terradot et al., 2005</a>).
Interaction 68: virB11_virB9
  • Input Objects: virB11, virB9
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: Analysis of protein-protein interactions by affinity precipitation revealed that VirB1 bound to VirB9 and VirB11 (<a href="#reference5727">Hoppner et al., 2005</a>).
Interaction 69: virB8_virB9
  • Input Objects: virB8, virB9
  • GO Evidence Code: Inferred from Physical Interaction
  • Description: VirB8 can interact with many other T4SS proteins including VirB10, VirB9, VirB1, VirB4, and VirB11, as well as with itself (<a href="#reference5729">Terradot et al., 2005</a>).
Interaction 70: xerD_xerC
  • Input Objects: xerD, xerC
  • GO Evidence Code: Traceable Author Statement
  • Description: The binding of both recombinases , xerC and xerD , is highly cooperative and protein-protein interactions are important to cleave DNA efficiently (<a href="#reference5736">Canavessi et al., 2004</a>)(<a href="#reference5737">Blakely et al., 1997</a>).
Pathways