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BMEII0681  -  virulence protein

Brucella melitensis bv. 1 str. 16M

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Disease relevance of BMEII0681

  • Comparison of B. suis with Brucella melitensis has defined a finite set of differences that could be responsible for the differences in virulence and host preference between these organisms, and indicates that phage have played a significant role in their divergence [1].
  • Brucella CbetaG is thus a virulence factor that interacts with lipid rafts and contributes to pathogen survival [2].
  • 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, Yersinia enterocolitica, and Pseudomonas aeruginosa [3].
  • Thus, IRF-1(-/-) mice are important to determining the level of Brucella virulence, to evaluating Brucella mutants for attenuation, and to investigating adaptive immunity in brucellosis [4].
  • These studies have identified two genes of potential importance in otitis media virulence [5].

High impact information on BMEII0681


Chemical compound and disease context of BMEII0681


Biological context of BMEII0681

  • The virB operon of Brucella abortus codes for a T4SS essential for virulence and intracellular multiplication [15].
  • To better characterize the role of O antigen in virulence and survival, transposon mutagenesis was used to generate B. abortus rough mutants defective in O-antigen presentation [16].
  • Several polysaccharides have been identified as important virulence factors, and the discovery of a novel polysaccharide in the brucellae which is probably not synthesized in B. abortus might be interesting for a better understanding of the pathogenicity and host preference differences observed between the Brucella species [17].
  • Sequence analysis of DNA flanking the site of transposon showed various insertion sites of bacterial genes that are virulence-associated genes, including virB genes, an ion transporter system, and biosynthesis- and metabolism-associated genes [18].
  • Despite being nonmotile, the brucellae contain flagellum gene clusters and display species-specific flagellar gene inactivations, which lead to the putative generation of different versions of flagellum-derived structures and may contribute to differences in host specificity and virulence [19].

Anatomical context of BMEII0681

  • Although not to the same extent, both mutants display reduced virulence in mice and defective intracellular multiplication in HeLa cells [20].
  • Expression of the virB operon, encoding the type IV secretion system required for Brucella suis virulence, occurred in the acidic phagocytic vacuoles of macrophages and could be induced in minimal medium at acidic pH values [21].
  • BALB/c mice were infected with strains 2308 and PHE1 to assess the effect of the htrA mutation on virulence, and significantly fewer brucellae were recovered from the spleens of mice infected with PHE1 than from those of mice infected with 2308 at 1 week postinfection [22].
  • Engulfment of all Brucella organisms (regardless of bacterial viability or virulence) initially resulted in phagosomes with tightly apposed walls (TP) [23].
  • Conventional typing, oxidative metabolic, and virulence tests were conducted on a phage-resistant Brucella abortus strain isolated from the supramammary lymph node of a cow [24].

Associations of BMEII0681 with chemical compounds

  • The ery operon encodes enzymes involved in erythritol metabolism, and a link with virulence has since been discussed [25].
  • These findings indicate that the 14-kDa protein of B. abortus possesses lectin-like properties and is essential for the virulence of the species, probably because of its direct or indirect role in the synthesis of smooth LPS [26].
  • In addition to being toxic, the phenol-soluble lipopolysaccharide may be a key virulence factor in intracellular survival of B. obortus within phagocytic cells [27].
  • Cyclic glucan is required in B. abortus for effective host interaction and complete expression of virulence [28].
  • It was hypothesized that DHBA is vital for bacterial virulence by its ability to chelate intracellular iron thereby preventing generation of anti-bacterial hydroxyl radicals via the Haber-Weiss reaction, to scavenge reactive oxygen intermediates and for acquisition of iron needed for nutritional purposes [29].

Other interactions of BMEII0681


Analytical, diagnostic and therapeutic context of BMEII0681

  • To understand the mechanism of virulence in B. melitensis, the proteome of vaccine strain Rev 1 was analyzed by two-dimensional gel electrophoresis and compared to that of virulent strain 16M [33].
  • The residual virulence and immunogenicity of both mutants were compared to the parental Rev.1 strain in sheep after subcutaneous or conjunctival vaccination [34].
  • Brucella abortus INTA2, a novel mutant strain, was constructed by inactivation of two B. abortus S19 genes: bp26 and bmp18, with the objective of obtaining a mutant strain that could be compatible with a diagnostic test and have less residual virulence than strain 19 [35].
  • Virulence may be expressed by a bacterial count in selected tissue of an animal host inoculated and autopsied in specified conditions [36].


  1. The Brucella suis genome reveals fundamental similarities between animal and plant pathogens and symbionts. Paulsen, I.T., Seshadri, R., Nelson, K.E., Eisen, J.A., Heidelberg, J.F., Read, T.D., Dodson, R.J., Umayam, L., Brinkac, L.M., Beanan, M.J., Daugherty, S.C., Deboy, R.T., Durkin, A.S., Kolonay, J.F., Madupu, R., Nelson, W.C., Ayodeji, B., Kraul, M., Shetty, J., Malek, J., Van Aken, S.E., Riedmuller, S., Tettelin, H., Gill, S.R., White, O., Salzberg, S.L., Hoover, D.L., Lindler, L.E., Halling, S.M., Boyle, S.M., Fraser, C.M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  2. Cyclic beta-1,2-glucan is a Brucella virulence factor required for intracellular survival. Arellano-Reynoso, B., Lapaque, N., Salcedo, S., Briones, G., Ciocchini, A.E., Ugalde, R., Moreno, E., Moriyón, I., Gorvel, J.P. Nat. Immunol. (2005) [Pubmed]
  3. Conserved DegP protease in gram-positive bacteria is essential for thermal and oxidative tolerance and full virulence in Streptococcus pyogenes. Jones, C.H., Bolken, T.C., Jones, K.F., Zeller, G.O., Hruby, D.E. Infect. Immun. (2001) [Pubmed]
  4. Virulence criteria for Brucella abortus strains as determined by interferon regulatory factor 1-deficient mice. Ko, J., Gendron-Fitzpatrick, A., Ficht, T.A., Splitter, G.A. Infect. Immun. (2002) [Pubmed]
  5. Genomic subtraction followed by dot blot screening of Streptococcus pneumoniae clinical and carriage isolates identifies genetic differences associated with strains that cause otitis media. Pettigrew, M.M., Fennie, K.P. Infect. Immun. (2005) [Pubmed]
  6. Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum. Celli, J., de Chastellier, C., Franchini, D.M., Pizarro-Cerda, J., Moreno, E., Gorvel, J.P. J. Exp. Med. (2003) [Pubmed]
  7. Brucella stationary-phase gene expression and virulence. Roop, R.M., Gee, J.M., Robertson, G.T., Richardson, J.M., Ng, W.L., Winkler, M.E. Annu. Rev. Microbiol. (2003) [Pubmed]
  8. Dimerization and interactions of Brucella suis VirB8 with VirB4 and VirB10 are required for its biological activity. Paschos, A., Patey, G., Sivanesan, D., Gao, C., Bayliss, R., Waksman, G., O'callaghan, D., Baron, C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  9. Subversion and utilization of the host cell cyclic adenosine 5'-monophosphate/protein kinase A pathway by Brucella during macrophage infection. Gross, A., Bouaboula, M., Casellas, P., Liautard, J.P., Dornand, J. J. Immunol. (2003) [Pubmed]
  10. Role of the Brucella suis lipopolysaccharide O antigen in phagosomal genesis and in inhibition of phagosome-lysosome fusion in murine macrophages. Porte, F., Naroeni, A., Ouahrani-Bettache, S., Liautard, J.P. Infect. Immun. (2003) [Pubmed]
  11. The siderophore 2,3-dihydroxybenzoic acid is not required for virulence of Brucella abortus in BALB/c mice. Bellaire, B.H., Elzer, P.H., Baldwin, C.L., Roop, R.M. Infect. Immun. (1999) [Pubmed]
  12. Synthesis of phosphatidylcholine, a typical eukaryotic phospholipid, is necessary for full virulence of the intracellular bacterial parasite Brucella abortus. Conde-Alvarez, R., Grilló, M.J., Salcedo, S.P., de Miguel, M.J., Fugier, E., Gorvel, J.P., Moriyón, I., Iriarte, M. Cell. Microbiol. (2006) [Pubmed]
  13. The Ton system, an ABC transporter, and a universally conserved GTPase are involved in iron utilization by Brucella melitensis 16M. Danese, I., Haine, V., Delrue, R.M., Tibor, A., Lestrate, P., Stevaux, O., Mertens, P., Paquet, J.Y., Godfroid, J., De Bolle, X., Letesson, J.J. Infect. Immun. (2004) [Pubmed]
  14. Intact purine biosynthesis pathways are required for wild-type virulence of Brucella abortus 2308 in the BALB/c mouse model. Alcantara, R.B., Read, R.D., Valderas, M.W., Brown, T.D., Roop, R.M. Infect. Immun. (2004) [Pubmed]
  15. Integration host factor is involved in transcriptional regulation of the Brucella abortus virB operon. Sieira, R., Comerci, D.J., Pietrasanta, L.I., Ugalde, R.A. Mol. Microbiol. (2004) [Pubmed]
  16. Transposon-derived Brucella abortus rough mutants are attenuated and exhibit reduced intracellular survival. Allen, C.A., Adams, L.G., Ficht, T.A. Infect. Immun. (1998) [Pubmed]
  17. Molecular characterization of a Brucella species large DNA fragment deleted in Brucella abortus strains: evidence for a locus involved in the synthesis of a polysaccharide. Vizcaíno, N., Cloeckaert, A., Zygmunt, M.S., Fernández-Lago, L. Infect. Immun. (1999) [Pubmed]
  18. Isolation and characterization of mini-Tn5Km2 insertion mutants of Brucella abortus deficient in internalization and intracellular growth in HeLa cells. Kim, S., Watarai, M., Kondo, Y., Erdenebaatar, J., Makino, S., Shirahata, T. Infect. Immun. (2003) [Pubmed]
  19. Whole-genome analyses of speciation events in pathogenic Brucellae. Chain, P.S., Comerci, D.J., Tolmasky, M.E., Larimer, F.W., Malfatti, S.A., Vergez, L.M., Aguero, F., Land, M.L., Ugalde, R.A., Garcia, E. Infect. Immun. (2005) [Pubmed]
  20. Brucella abortus cyclic beta-1,2-glucan mutants have reduced virulence in mice and are defective in intracellular replication in HeLa cells. Briones, G., Iñón de Iannino, N., Roset, M., Vigliocco, A., Paulo, P.S., Ugalde, R.A. Infect. Immun. (2001) [Pubmed]
  21. Production of the type IV secretion system differs among Brucella species as revealed with VirB5- and VirB8-specific antisera. Rouot, B., Alvarez-Martinez, M.T., Marius, C., Menanteau, P., Guilloteau, L., Boigegrain, R.A., Zumbihl, R., O'Callaghan, D., Domke, N., Baron, C. Infect. Immun. (2003) [Pubmed]
  22. Characterization and genetic complementation of a Brucella abortus high-temperature-requirement A (htrA) deletion mutant. Elzer, P.H., Phillips, R.W., Kovach, M.E., Peterson, K.M., Roop, R.M. Infect. Immun. (1994) [Pubmed]
  23. Intracellular survival of Brucella spp. in human monocytes involves conventional uptake but special phagosomes. Rittig, M.G., Alvarez-Martinez, M.T., Porte, F., Liautard, J.P., Rouot, B. Infect. Immun. (2001) [Pubmed]
  24. Smooth phage-resistant Brucella abortus from bovine tissue. Harrington, R., Bond, D.R., Brown, G.M. J. Clin. Microbiol. (1977) [Pubmed]
  25. Analysis of the behavior of eryC mutants of Brucella suis attenuated in macrophages. Burkhardt, S., Jiménez de Bagüés, M.P., Liautard, J.P., Köhler, S. Infect. Immun. (2005) [Pubmed]
  26. Role in virulence of a Brucella abortus protein exhibiting lectin-like activity. Vemulapalli, T.H., Vemulapalli, R., Schurig, G.G., Boyle, S.M., Sriranganathan, N. Infect. Immun. (2006) [Pubmed]
  27. Surface macromolecules and virulence in intracellular parasitism: comparison of cell envelope components of smooth and rough strains of Brucella abortus. Kreutzer, D.L., Robertson, D.C. Infect. Immun. (1979) [Pubmed]
  28. Membrane topology analysis of cyclic glucan synthase, a virulence determinant of Brucella abortus. Ciocchini, A.E., Roset, M.S., Iñón de Iannino, N., Ugalde, R.A. J. Bacteriol. (2004) [Pubmed]
  29. Brucella abortus siderophore 2,3-dihydroxybenzoic acid (DHBA) facilitates intracellular survival of the bacteria. Parent, M.A., Bellaire, B.H., Murphy, E.A., Roop, R.M., Elzer, P.H., Baldwin, C.L. Microb. Pathog. (2002) [Pubmed]
  30. The identification of two protective DNA vaccines from a panel of five plasmid constructs encoding Brucella melitensis 16M genes. Commander, N.J., Spencer, S.A., Wren, B.W., Macmillan, A.P. Vaccine (2007) [Pubmed]
  31. Attenuated bioluminescent Brucella melitensis mutants GR019 (virB4), GR024 (galE), and GR026 (BMEI1090-BMEI1091) confer protection in mice. Rajashekara, G., Glover, D.A., Banai, M., O'Callaghan, D., Splitter, G.A. Infect. Immun. (2006) [Pubmed]
  32. Role of catalase in the virulence of Brucella melitensis in pregnant goats. Gee, J.M., Kovach, M.E., Grippe, V.K., Hagius, S., Walker, J.V., Elzer, P.H., Roop, R.M. Vet. Microbiol. (2004) [Pubmed]
  33. Comparative proteome analysis of Brucella melitensis vaccine strain Rev 1 and a virulent strain, 16M. Eschenbrenner, M., Wagner, M.A., Horn, T.A., Kraycer, J.A., Mujer, C.V., Hagius, S., Elzer, P., DelVecchio, V.G. J. Bacteriol. (2002) [Pubmed]
  34. Residual virulence and immunogenicity of CGV26 and CGV2631 B. melitensis Rev. 1 deletion mutant strains in sheep after subcutaneous or conjunctival vaccination. Guilloteau, L.A., Laroucau, K., Olivier, M., Grillo, M.J., Marin, C.M., Verger, J.M., Blasco, J.M. Vaccine (2006) [Pubmed]
  35. Brucella abortus INTA2, a novel strain 19 (Delta)bp26::luc (Delta)bmp18 double mutant lacking drug resistance markers. Campos, E., Cravero, S.L., Delgui, L., Mora, I., Kahn, N., Arese, A.I., Rossetti, O.L. Vet. Microbiol. (2002) [Pubmed]
  36. Virulence of Brucella: bacterial growth and decline in mice. Plommet, M., Plommet, A.M. Ann. Rech. Vet. (1988) [Pubmed]
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