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fmtA  encodes a low-affinity penicillin binding protein in  Staphylococcus aureus . It is part of the core cell wall stimulon and is involved in methicillin resistance in  S. aureus . Here, we report that the transcription factor, SarA, a pleiotropic regulator of virulence genes in  S. aureus,  regulates the expression of  fmtA .  In vitro  binding studies with purified SarA revealed that it binds to specific sites within the 541-bp promoter region of  fmtA . Mutation of a key residue of the regulatory activity of SarA (Arg90) abolished binding of SarA to the  fmtA  promoter, suggesting that SarA binds specifically to the  fmtA  promoter region.  In vivo  analysis of the  fmtA  promoter using a  lux operon  reporter fusion show high level expression following oxacillin induction, which was abrogated in a  sarA  mutant strain. These data suggest that SarA is essential for the induction of  fmtA  expression by cell wall-specific antibiotics. Further,  in vitro  transcription studies show that SarA enhances  fmtA  transcription and suggest that regulation of  fmtA  could be via a SigA-dependent mechanism. Overall, our results show that SarA plays a direct role in the regulation of  fmtA  expression via binding to the  fmtA  promoter.

Staphylococcus aureus Methicillin-Resistance Factor fmtA Is Regulated by the Global Regulator SarA