has role has_role has role gene as virulence factor in pathogen gene mutant attenuated in host cell line cell gene mutant attenuated in host cell gene mutant attenuated in host has role has_role has role HeLa cell HeLa cell HeLa 细胞 epithelial cell epithelial cell 上皮细胞 macrophage macrophage 巨噬细胞 Mus musculus Mus musculus 小家鼠 Brucella melitensis bv. 1 str. 16M protein-coding gene of Brucella melitensis bv. 1 str. 16M BMEI2035 1197746 20140217 224914 BMEI2035 Bin Zhao, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sensor protein CHVG 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 [PMID:11401996]. 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 [PMID:11401996]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [PMID:11401996]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [PMID: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 [PMID:11401996]. 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 [PMID:11401996]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [PMID:11401996]. 1323 virulence factor gene role