title: Acquisition of VanB-type vancomycin resistance by Bacillus subtilis: the impact on gene expression, cell wall composition and morphology.
abstract: The vancomycin resistance operons from Enterococci, Staphylococci and Actinomycetes encode a VanRS two-component signal transduction system (TCS) and a suite of enzymes to modify the peptidoglycan biosynthetic precursor lipid II and to eliminate the D-Ala-D-Ala from the cell. Commingling of these regulatory and enzymatic activities with host functions has the potential to significantly impact host gene expression and cell wall metabolism. Here we report the effects of individually expressing the VanR(B) S(B) TCS and the VanY(B) WH(B) BX(B) resistance proteins in Bacillus subtilis. VanY(B) WH(B) BX(B) expression confers resistance to 2 µg ml(-1) of vancomycin with concomitant reduced Van-FL staining and leads to a cell division defect. In contrast to E. faecalis and S. aureus, VanS(B) is active in B. subtilis without vancomycin addition. Individual expression of the VanR(B) S(B) TCS and the VanY(B) WH(B) BX(B) resistance proteins repress and increase, respectively, expression of PhoPR regulon genes in the phosphate-limited state. When vancomycin-resistant cells are exposed to elevated vancomycin levels, mutant strains with increased resistance to vancomycin and a growth dependency on vanY(B) WH(B) BX(B) expression frequently arise. Mutation of the endogenous Ddl ligase is the necessary and sufficient cause of both phenotypes. We discuss how these effects may influence establishment of van operons in new host bacteria.
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Paola
authors.initials: P
authors.lastname: Bisicchia
authors.forename: Nhat Khai
authors.initials: NK
authors.lastname: Bui
authors.forename: Christine
authors.initials: C
authors.lastname: Aldridge
authors.forename: Waldemar
authors.initials: W
authors.lastname: Vollmer
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Devine
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001412:Bacillus subtilis / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000737:chemistry* / Q000378:metabolism; D013293:Enterococcus faecalis / Q000235:genetics; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D009876:Operon; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013210:Staphylococcus / Q000235:genetics; D014640:Vancomycin / Q000494:pharmacology*; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D014640:Vancomycin