JB Accepts, published online ahead of print on 23 October 2009

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J. Bacteriol. doi:10.1128/JB.01202-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Control of thioredoxin reductase (trxB) transcription by SarA in Staphylococcus aureus

Anand Ballal and Adhar C. Manna^*

Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota 57069; and Center for Infectious Disease Research and Vaccinology, South Dakota State University, Brookings, South Dakota 57007

^* To whom correspondence should be addressed. Email: amanna{at}usd.edu.

The thioredoxin reductase (encoded by trxB) protects S. aureus against oxygen or disulfide stress and is indispensible for growth. Among the different sarA family mutants analyzed, transcription of trxB was markedly elevated in the sarA mutant under conditions of aerobic, as well as micro-aerophilic growth, indicating that SarA acts as a negative regulator of trxB expression. Gel shift analysis showed that purified SarA protein binds directly to the trxB promoter region DNA in vitro. DNA binding of SarA was essential for repression of trxB transcription in vivo in S. aureus. Northern blot analysis and DNA binding studies of the purified wild-type SarA and the mutant SarAC9G with oxidizing agents indicated that oxidation of Cys-9 reduced the binding of SarA to the trxB promoter DNA. Oxidizing agents, in particular diamide could further enhance transcription of the trxB gene in the sarA mutant suggesting the presence of a SarA-independent mode of trxB induction. Analysis of two oxidative stress-responsive sarA-regulatory target genes, trxB and sodM, with various mutant sarA constructs showed differential ability of the SarA to regulate expression of the two above-mentioned genes in vivo. The overall data demonstrates the important role played by SarA in modulating expression of genes involved in oxidative stress resistance in S. aureus.