VraSR two-component regulatory system and its role in induction of pbp2 and vraSR expression by cell wall antimicrobials in Staphylococcus aureus

The VraS/VraR two-component system (VraSR) regulates transcriptional induction of penicillin-binding protein 2 (encoded by pbp2) by vancomycin in Staphylococcus aureus. We have now defined the vraSR operon and determined that its induction by beta-lactams as well as by vancomycin is autoregulated. Induction of the pbp2 and vraSR operons by beta-lactams and related compounds within 1 hour after exposure to the antimicrobials was dependent on vraS. However, when a disk diffusion assay that can detect induction of genes over an extended time period was used, induction of the pbp2 operon was mediated by some beta-lactams, including oxacillin; this induction was independent of vraS.