title: Genome-wide analysis of the regulatory function mediated by the small regulatory psm-mec RNA of methicillin-resistant Staphylococcus aureus.
abstract: Several methicillin resistance (SCCmec) clusters characteristic of hospital-associated methicillin-resistant Staphylococcus aureus (MRSA) strains harbor the psm-mec locus. In addition to encoding the cytolysin, phenol-soluble modulin (PSM)-mec, this locus has been attributed gene regulatory functions. Here we employed genome-wide transcriptional profiling to define the regulatory function of the psm-mec locus. The immune evasion factor protein A emerged as the primary conserved and strongly regulated target of psm-mec, an effect we show is mediated by the psm-mec RNA. Furthermore, the psm-mec locus exerted regulatory effects that were more moderate in extent. For example, expression of PSM-mec limited expression of mecA, thereby decreasing methicillin resistance. Our study shows that the psm-mec locus has a rare dual regulatory RNA and encoded cytolysin function. Furthermore, our findings reveal a specific mechanism underscoring the recently emerging concept that S. aureus strains balance pronounced virulence and high expression of antibiotic resistance.
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD, USA.
authors.forename: Gordon Y C
authors.initials: GY
authors.lastname: Cheung
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD, USA.
authors.forename: Amer E
authors.initials: AE
authors.lastname: Villaruz
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD, USA.
authors.forename: Hwang-Soo
authors.initials: HS
authors.lastname: Joo
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD, USA.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Duong
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Yeh
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD, USA.
authors.forename: Thuan H
authors.initials: TH
authors.lastname: Nguyen
authors.affiliation: Genomics Unit, Research Technology Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Hamilton, MT, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Sturdevant
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Queck
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD, USA. Electronic address: motto@niaid.nih.gov.
authors.forename: M
authors.initials: M
authors.lastname: Otto
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis; D001427:Bacterial Toxins / Q000096:biosynthesis; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000302:isolation & purification; D046915:Penicillin-Binding Proteins; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000382:microbiology; D013205:Staphylococcal Protein A / Q000096:biosynthesis
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D046915:Penicillin-Binding Proteins; D034741:RNA, Small Interfering; D013205:Staphylococcal Protein A; C487789:mecA protein, Staphylococcus aureus; C025971:staphylococcal delta toxin
keywords: Antibiotic resistance; MRSA; Staphylococcus aureus; Virulence