title: Staphylococcus aureus methicillin-resistance factor fmtA is regulated by the global regulator SarA.
abstract: 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.
authors.affiliation: Department of Chemistry, York University, Toronto, Ontario, Canada.
authors.forename: Yinglu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Vidhu
authors.initials: V
authors.lastname: Verma
authors.forename: Antoaneta
authors.initials: A
authors.lastname: Belcheva
authors.forename: Atul
authors.initials: A
authors.lastname: Singh
authors.forename: Michael
authors.initials: M
authors.lastname: Fridman
authors.forename: Dasantila
authors.initials: D
authors.lastname: Golemi-Kotra
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D004269:DNA, Bacterial / Q000235:genetics; D003850:Deoxyribonuclease I / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D016106:Methicillin Resistance / Q000235:genetics*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009876:Operon / Q000235:genetics; D046915:Penicillin-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; C526198:FmtA protein, Staphylococcus aureus; D046915:Penicillin-Binding Proteins; D012333:RNA, Messenger; C492107:SarA protein, Staphylococcus aureus; D014157:Transcription Factors; D003850:Deoxyribonuclease I