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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-46068

McCallum, N; Stutzmann Meier, P; Heusser, R; Berger-Bächi, B (2011). Mutational analyses of ORFs within the vraSR operon and their roles in the cell wall stress response of Staphylococcus aureus. Antimicrobial Agents and Chemotherapy, 55(4):1391-1402.

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Exposure of Staphylococcus aureus to a broad range of cell wall-damaging agents, triggers the induction of a cell wall stress stimulon (CWSS), controlled by the VraSR two-component system. The vraSR genes form part of the four-cistronic autoregulatory operon, orf1-yvqF-vraS-vraR. Markerless inactivation of each of the genes within this operon revealed that orf1 played no observable role in CWSS induction and had no influence on resistance phenotypes for any of the cell envelope stress-inducing agents tested. The remaining three genes were all essential for induction of the CWSS and mutants showed varying degrees of increased susceptibility to cell wall active antibiotics. Therefore, the role of YvqF in S. aureus appears to be opposite to that in other Gram-positive bacteria, where YvqF homologs have all been shown to inhibit signal transduction. This role, as an activator rather than repressor of signal transduction, corresponds well with resistance phenotypes of ΔYvqF mutants, which were similar to those of ΔVraR mutants in which CWSS induction was also completely abolished. Resistance profiles of ΔVraS mutants differed phenotypically from those of ΔYvqF and ΔVraR mutants on many non-ß-lactam antibiotics. ΔVraS mutants still became more susceptible than wild type strains at low antibiotic concentrations, but retained larger subpopulations able to grow on higher antibiotic concentrations than ΔYvqF and ΔVraR mutants. Subpopulations of ΔVraS mutants could grow on even higher glycopeptide concentrations than wild type strains. Expression of a highly sensitive CWSS-luciferase reporter gene fusion, was up to 2.6-fold higher in a ΔVraS than a ΔVraR mutant, which could be linked to differences in their respective antibiotic resistance phenotypes. Bacterial two-hybrid analysis indicated that the integral membrane protein YvqF interacted directly with VraS but not VraR, suggesting that it plays an essential role in sensing the as yet unknown trigger of CWSS induction.


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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Microbiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Deposited On:10 Mar 2011 15:50
Last Modified:05 Apr 2016 14:47
Publisher:American Society for Microbiology
Publisher DOI:10.1128/AAC.01213-10
PubMed ID:21220524

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