title: Transcription and translation products of the cytolysin gene psm-mec on the mobile genetic element SCCmec regulate Staphylococcus aureus virulence.
abstract: The F region downstream of the mecI gene in the SCCmec element in hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) contains two bidirectionally overlapping open reading frames (ORFs), the fudoh ORF and the psm-mec ORF. The psm-mec ORF encodes a cytolysin, phenol-soluble modulin (PSM)-mec. Transformation of the F region into the Newman strain, which is a methicillin-sensitive S. aureus (MSSA) strain, or into the MW2 (USA400) and FRP3757 (USA300) strains, which are community-acquired MRSA (CA-MRSA) strains that lack the F region, attenuated their virulence in a mouse systemic infection model. Introducing the F region to these strains suppressed colony-spreading activity and PSMα production, and promoted biofilm formation. By producing mutations into the psm-mec ORF, we revealed that (i) both the transcription and translation products of the psm-mec ORF suppressed colony-spreading activity and promoted biofilm formation; and (ii) the transcription product of the psm-mec ORF, but not its translation product, decreased PSMα production. These findings suggest that both the psm-mec transcript, acting as a regulatory RNA, and the PSM-mec protein encoded by the gene on the mobile genetic element SCCmec regulate the virulence of Staphylococcus aureus.
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Kaito
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saito
authors.forename: Gentaro
authors.initials: G
authors.lastname: Nagano
authors.forename: Mariko
authors.initials: M
authors.lastname: Ikuo
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Omae
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hanada
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kuwahara-Arai
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hishinuma
authors.forename: Tadashi
authors.initials: T
authors.lastname: Baba
authors.forename: Teruyo
authors.initials: T
authors.lastname: Ito
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hiramatsu
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sekimizu
mesh_terms: D000818:Animals; D001483:Base Sequence; D005260:Female; D020071:Interspersed Repetitive Sequences / Q000235:genetics / Q000502:physiology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D030781:Organisms, Genetically Modified; D054353:Perforin / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D014176:Protein Biosynthesis / Q000502:physiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity*; D014158:Transcription, Genetic / Q000502:physiology; D014169:Transformation, Bacterial / Q000502:physiology; D014774:Virulence / Q000235:genetics
chemical_list: D054353:Perforin