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Journal of Bacteriology, May 2009, p. 2953-2963, Vol. 191, No. 9
0021-9193/09/$08.00+0     doi:10.1128/JB.01492-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

CodY in Staphylococcus aureus: a Regulatory Link between Metabolism and Virulence Gene Expression ^,

Konstanze Pohl,¹ Patrice Francois,² Ludwig Stenz,² Frank Schlink,¹ Tobias Geiger,¹ Silvia Herbert,³ Christiane Goerke,¹ Jacques Schrenzel,² and Christiane Wolz^1*

Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany,¹ Genomic Research Laboratory, Infectious Diseases Service, Geneva University Hospitals and the University of Geneva, CH-1211 Geneva 4, Switzerland,² Microbial Genetics, University of Tübingen, Tübingen, Germany³

Received 23 October 2008/ Accepted 16 February 2009

The repressor CodY is reported to inhibit metabolic genes mainly involved in nitrogen metabolism. We analyzed codY mutants from three unrelated Staphylococcus aureus strains (Newman, UAMS-1, and RN1HG). The mutants grew more slowly than their parent strains in a chemically defined medium. However, only codY mutants were able to grow in medium lacking threonine. An excess of isoleucine resulted in growth inhibition in the wild type but not in the codY mutants, indicating that isoleucine plays a role in CodY-dependent repression. Prototypic CodY-repressed genes including the virulence regulator agr are repressed after up-shift with isoleucine. The CodY-dependent repression of agr is consistent with the concomitant influence of CodY on typical agr-regulated genes such as cap, spa, fnbA, and coa. However, some of these virulence genes (e.g., cap, fnbA, and spa) were also regulated by CodY in an agr-negative background. Microarray analysis revealed that the large majority of CodY-repressed genes were involved in amino acid metabolism; CodY-activated genes were mainly involved in nucleotide metabolism or virulence. In summary, CodY in S. aureus not only acts as a repressor for genes involved in nitrogen metabolism but also contributes to virulence gene regulation by supporting as well as substituting for agr function.

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* Corresponding author. Mailing address: Institut für Medizinische Mikrobiologie und Hygiene, Universität Tübingen, Elfriede-Aulhornstraße 6, 72076 Tübingen, Germany. Phone: 49 7071 2980187. Fax: 49 7071 295165. E-mail: christiane.wolz{at}med.uni-tuebingen.de

Published ahead of print on 27 February 2009.

Supplemental material for this article may be found at http://jb.asm.org/.

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Journal of Bacteriology, May 2009, p. 2953-2963, Vol. 191, No. 9
0021-9193/09/$08.00+0     doi:10.1128/JB.01492-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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