title: Mobile genetic element SCCmec-encoded psm-mec RNA suppresses translation of agrA and attenuates MRSA virulence.
abstract: Community acquired-methicillin resistant Staphylococcus aureus (CA-MRSA) is a socially problematic pathogen that infects healthy individuals, causing severe disease. CA-MRSA is more virulent than hospital associated-MRSA (HA-MRSA). The underlying mechanism for the high virulence of CA-MRSA is not known. The transcription product of the psm-mec gene, located in the mobile genetic element SCCmec of HA-MRSA, but not CA-MRSA, suppresses the expression of phenol-soluble modulin α (PSMα), a cytolytic toxin of S. aureus. Here we report that psm-mec RNA inhibits translation of the agrA gene encoding a positive transcription factor for the PSMα gene via specific binding to agrA mRNA. Furthermore, 25% of 325 clinical MRSA isolates had a mutation in the psm-mec promoter that attenuated transcription, and 9% of the strains had no psm-mec. In most of these psm-mec-mutated or psm-mec-deleted HA-MRSAs, PSMα expression was increased compared with strains carrying intact psm-mec, and some mutated strains produced high amounts of PSMα comparable with that of CA-MRSA. Deletion of psm-mec from HA-MRSA strains carrying intact psm-mec increased the expression of AgrA protein and PSMα, and virulence in mice. Thus, psm-mec RNA suppresses MRSA virulence via inhibition of agrA translation and the absence of psm-mec function in CA-MRSA causes its high virulence property.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan. kaito@mol.f.u-tokyo.ac.jp
authors.forename: Chikara
authors.initials: C
authors.lastname: Kaito
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saito
authors.forename: Mariko
authors.initials: M
authors.lastname: Ikuo
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Omae
authors.forename: Han
authors.initials: H
authors.lastname: Mao
authors.forename: Gentaro
authors.initials: G
authors.lastname: Nagano
authors.forename: Tomoko
authors.initials: T
authors.lastname: Fujiyuki
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Numata
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Obata
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Koiti
authors.initials: K
authors.lastname: Inokuchi
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; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000235:genetics*; D017714:Community-Acquired Infections / Q000382:microbiology; D005260:Female; D020071:Interspersed Repetitive Sequences; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity*; D051379:Mice; D009154:Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013207:Staphylococcal Skin Infections / Q000382:microbiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D001427:Bacterial Toxins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D014157:Transcription Factors; C025971:staphylococcal delta toxin