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Antimicrobial Agents and Chemotherapy, August 2004, p. 3057-3063, Vol. 48, No. 8
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.8.3057-3063.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Regulation of the Expression of Cell Wall Stress Stimulon Member Gene msrA1 in Methicillin-Susceptible or -Resistant Staphylococcus aureus

Roger Pechous, Nagender Ledala, Brian J. Wilkinson, and Radheshyam K. Jayaswal*

Microbiology Group, Department of Biological Sciences, Illinois State University, Normal, Illinois 61790-4120

Received 7 October 2003/ Returned for modification 19 December 2003/ Accepted 1 April 2004

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.

* Corresponding author. Mailing address: Department of Biological Sciences, Illinois State University, Normal, IL 61790-4120. Phone: (309) 438-5128. Fax: (309) 438-3722. E-mail: drjay{at}ilstu.edu.

Antimicrobial Agents and Chemotherapy, August 2004, p. 3057-3063, Vol. 48, No. 8
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.8.3057-3063.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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