title: Subinhibitory concentrations of beta-lactam induce haemolytic activity in Staphylococcus aureus through the SaeRS two-component system.
abstract: SaeRS is a two-component system that has been characterized as a positive regulatory system for the expression of several virulence factors, including coagulase, alpha-, beta- and gamma-haemolysins, nuclease, and fibronectin-binding proteins in Staphylococcus aureus. Previously, the SaeRS system was found to be induced at the transcriptional level by beta-lactam. Here, we found that subinhibitory concentrations of beta-lactam induce haemolytic activity in the S. aureus N315 strain but not in the saeRS null mutant KSA. Comparison of the transcriptional profile of the N315 and KSA strains by microarray analysis reveals that the SaeRS system modulates the regulation of coagulase (coa), alpha-, beta- and gamma-haemolysins (hla, hlb and hlg), nuclease (SA0746), fibrinogen-binding proteins (emp, efb, SA1000 and SA1004), fibronectin-binding protein B (fnbB), and 13 other genes. Further, the use of cefoxitin as a signal inducer reveals that the SaeRS system appears to modulate 22 additional genes as a secondary regulon, including the staphylococcal accessory regulators SarA and SarT and the Clp protease ATPase subunits ClpB and ClpL. These observations suggest that beta-lactam is able to induce the SaeRS system, which acts as a crucial signal transduction system for S. aureus pathogenicity rather than antimicrobial resistance.
authors.affiliation: Department of Bacteriology, Juntendo University, Hongo, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kuroda
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuroda
authors.forename: Longzhu
authors.initials: L
authors.lastname: Cui
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hiramatsu
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002440:Cefoxitin / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity*; D014157:Transcription Factors; D014774:Virulence; D037521:Virulence Factors; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D006460:Hemolysin Proteins; C433805:SaeR protein, Staphylococcus aureus; D014157:Transcription Factors; D037521:Virulence Factors; D047090:beta-Lactams; D002440:Cefoxitin