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Journal of Bacteriology, January 2004, p. 326-334, Vol. 186, No. 2
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.2.326-334.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Transcriptional Regulation of the Staphylococcus aureus Thioredoxin and Thioredoxin Reductase Genes in Response to Oxygen and Disulfide Stress

Orit Uziel,{dagger} Ilya Borovok, Rachel Schreiber, Gerald Cohen, and Yair Aharonowitz*

Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel

Received 21 July 2003/ Accepted 8 October 2003

In this report we describe the cloning, organization, and promoter analysis of the Staphylococcus aureus thioredoxin (trxA) and thioredoxin reductase (trxB) genes and their transcription in response to changes in oxygen concentration and to oxidative stress compounds. Northern analysis showed that the S. aureus trxA and trxB genes were transcribed equally well in aerobic and anaerobic conditions. Several oxidative stress compounds were found to rapidly induce transcription of the trxA and trxB genes. The most pronounced effects were seen with diamide, a thiol-specific oxidant that promotes disulfide bond formation; menadione, a redox cycling agent; and {tau}-butyl hydroperoxide, an organic peroxide. In each case the induction was independent of the general stress sigma factor {sigma}B. These studies show that the S. aureus trxA and trxB genes are upregulated following exposure to these oxidative stress agents, resulting in increased disulfide bond formation. In contrast, no effect of hydrogen peroxide on induction of the trxA and trxB genes was seen. We also show that the S. aureus thioredoxin reductase appears to be essential for growth. This observation, coupled with structural differences between the bacterial and mammalian thioredoxin reductases, suggests that it may serve as a target for the development of new antimicrobials.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel. Phone: 972-3-6409411. Fax: 972-3-6422245. E-mail: yaira{at}post.tau.ac.il.

{dagger} Present address: Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.

Journal of Bacteriology, January 2004, p. 326-334, Vol. 186, No. 2
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.2.326-334.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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