Identification of a Novel Two-Component Regulatory System That Acts in Global Regulation of Virulence Factors ofStaphylococcus aureus

• DOI: 10.1128/jb.183.4.1113-1123.2001
• Publication Date: 2002-07-27T10:01:09Z
• Authors: Jeremy M. Yarwood; John K. McCormick; Patrick M. Schlie...
• Keywords: Staphylococcus aureus; 0303 health sciences; Superantigens; Base Sequence; Virulence; Gene Expression Profiling; Bacterial Toxins; Molecular Sequence Data; Gene Expression Regulation, Bacterial; Aerobiosis; 3. Good health; Repressor Proteins; Enterotoxins; 03 medical and health sciences; Bacterial Proteins; Mutagenesis; Amino Acid Sequence; Anaerobiosis; Signal Transduction

ABSTRACTWe have previously demonstrated that the presence of oxygen is necessary for the production of toxic shock syndrome toxin 1 (TSST-1) byStaphylococcus aureusin vitro. To investigate the mechanism by which oxygen might regulate toxin production, we identified homologs inS. aureusof theBacillus subtilis resDEgenes. The two-component regulatory system encoded byresDE, ResD-ResE, has been implicated in the global regulation of aerobic and anaerobic respiratory metabolism inB. subtilis. We have designated theS. aureushomologssrrAB(staphylococcal respiratory response). The effects ofsrrABexpression on expression of RNAIII (the effector molecule of theagrlocus) and on production of TSST-1 (an exotoxin) and protein A (a surface-associated virulence factor) were investigated. Expression of RNAIII was inversely related to expression ofsrrAB. Disruption ofsrrBresulted in increased levels of RNAIII, while expression ofsrrABintranson a multicopy plasmid resulted in repression of RNAIII transcription, particularly in microaerobic conditions. Disruption ofsrrBresulted in decreased production of TSST-1 under microaerobic conditions and, to a lesser extent, under aerobic conditions as well. Overexpression ofsrrABresulted in nearly complete repression of TSST-1 production in both microaerobic and aerobic conditions. Protein A production by thesrrBmutant was upregulated in microaerobic conditions and decreased in aerobic conditions. Protein A production was restored to nearly wild-type levels by complementation ofsrrABinto the null mutant. These results indicate that the putative two-component system encoded bysrrAB, SrrA-SrrB, acts in the global regulation of staphylococcal virulence factors, and may repress virulence factors under low-oxygen conditions. Furthermore,srrABmay provide a mechanistic link between respiratory metabolism, environmental signals, and regulation of virulence factors inS. aureus.