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Acquisition of VanB-type vancomycin resistance by Bacillus subtilis: the impact on gene expression, cell wall composition and morphology

Lookup NU author(s): Dr Nhat Khai Bui, Christine Aldridge, Professor Waldemar Vollmer


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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 mu g 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.

Publication metadata

Author(s): Bisicchia P, Bui NK, Aldridge C, Vollmer W, Devine KM

Publication type: Article

Publication status: Published

Journal: Molecular Microbiology

Year: 2011

Volume: 81

Issue: 1

Pages: 157-178

Print publication date: 19/05/2011

ISSN (print): 0950-382X

ISSN (electronic): 1365-2958

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/j.1365-2958.2011.07684.x


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Funder referenceFunder name
Biotechnology and Biological Sciences Research Council (BBSRC)
08/IN.1/B1859Science Foundation Ireland