Regulation of the expression of cell wall stress stimulon member gene msrA1 in methicillin-susceptible or -resistant Staphylococcus aureus

Genome-wide transcriptional profiling studies of the response of Staphylococcus aureus to cell wall-active antibiotics have led to the discovery of a cell wall stress stimulon of genes induced by these agents. msrA1, encoding methionine sulfoxide reductase, is a highly induced member gene of this stimulon. In the present study we show that msrA1 induction by oxacillin is common to all methicillin-susceptible strains studied but did not occur in two homogeneous and two heterogeneous methicillin-resistant strains. However, msrA1 was induced by vancomycin and/or D-cycloserine in methicillin-resistant strains. Lysozyme and lysostaphin treatment did not induce msrA1 expression. Oxacillin-induced msrA1 expression was enhanced by ca. 30% in a SigB(+) derivative (SH1000) of the SigB-defective RN450 (NCTC 8325-4) strain. msrA1 expression was not affected in mutants in the global regulatory systems agr and sar. Glycerol monolaurate, an inhibitor of signal transduction, inhibited the oxacillin-induced transcription of msrA1 and other cell wall stress stimulon member genes, vraS and dnaK. These observations suggest that the cell wall stress stimulon is induced by inhibition of the process of peptidoglycan biosynthesis, and the inhibitory effects of glycerol monolaurate indicate that gene expression is dependent on a signal transduction pathway.