title: Distribution and regulation of the mobile genetic element-encoded phenol-soluble modulin PSM-mec in methicillin-resistant Staphylococcus aureus.
abstract: The phenol-soluble modulin PSM-mec is the only known staphylococcal toxin that is encoded on a mobile antibiotic resistance determinant, namely the staphylococcal cassette chromosome (SCC) element mec encoding resistance to methicillin. Here we show that the psm-mec gene is found frequently among methicillin-resistant Staphylococcus aureus (MRSA) strains of SCCmec types II, III, and VIII, and is a conserved part of the class A mec gene complex. Controlled expression of AgrA versus RNAIII in agr mutants of all 3 psm-mec-positive SCCmec types demonstrated that expression of psm-mec, which is highly variable, is controlled by AgrA in an RNAIII-independent manner. Furthermore, psm-mec isogenic deletion mutants showed only minor changes in PSMα peptide production and unchanged (or, as previously described, diminished) virulence compared to the corresponding wild-type strains in a mouse model of skin infection. This indicates that the recently reported regulatory impact of the psm-mec locus on MRSA virulence, which is opposite to that of the PSM-mec peptide and likely mediated by a regulatory RNA, is minor when analyzed in the original strain background. Our study gives new insight in the distribution, regulation, and role in virulence of the PSM-mec peptide and the psm-mec gene locus.
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Som S
authors.initials: SS
authors.lastname: Chatterjee
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Hwang-Soo
authors.initials: HS
authors.lastname: Joo
authors.forename: Gordon Y C
authors.initials: GY
authors.lastname: Cheung
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
mesh_terms: D000038:Abscess / Q000382:microbiology; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D004195:Disease Models, Animal; D005798:Genes, Bacterial / Q000235:genetics*; D020071:Interspersed Repetitive Sequences / Q000235:genetics*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D010455:Peptides; C025971:staphylococcal delta toxin