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

• DOI: 10.1128/jb.01492-08
• Publication Date: 2009-02-28T02:11:02Z
• Authors: Konstanze Pohl; Patrice Francois; Ludwig Stenz; Frank Schlink; Tobias Geiger; Silvia Herbert; Christiane Goerke; Jacques Schrenzel; Christiane Wolz
• Keywords: Threonine; 0301 basic medicine; Staphylococcus aureus; Virulence Factors; Virulence Factors/biosynthesis; 03 medical and health sciences; Bacterial Proteins; info:eu-repo/classification/ddc/616; Isoleucine; Bacterial Proteins/biosynthesis/genetics/physiology; Oligonucleotide Array Sequence Analysis; ddc:616; 0303 health sciences; Virulence; Gene Expression Profiling; Trans-Activators/biosynthesis; Gene Expression Regulation, Bacterial; Isoleucine/metabolism; Staphylococcus aureus/metabolism/pathogenicity/physiology; 3. Good health; Repressor Proteins; Mutation; Trans-Activators; Threonine/metabolism; Repressor Proteins/genetics/physiology

ABSTRACT

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.