Mobile Genetic Element SCCmec-encoded psm-mec RNA Suppresses Translation of agrA and Attenuates MRSA Virulence

Chikara Kaito, Yuki Saito, Mariko Ikuo, Yosuke Omae, Han Mao, Gentaro Nagano, Tomoko Fujiyuki, Shunsuke Numata, Xiao Han, Kazuaki Obata, Setsuo Hasegawa, Hiroki Yamaguchi, Koiti Inokuchi, Teruyo Ito, Keiichi Hiramatsu, Kazuhisa Sekimizu

Research output: Contribution to journalArticle

59 Citations (Scopus)

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.

Original languageEnglish
Article numbere1003269
JournalPLoS Pathogens
Volume9
Issue number4
DOIs
Publication statusPublished - Apr 1 2013
Externally publishedYes

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Interspersed Repetitive Sequences
Methicillin-Resistant Staphylococcus aureus
Virulence
RNA
Genes
Staphylococcus aureus

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Mobile Genetic Element SCCmec-encoded psm-mec RNA Suppresses Translation of agrA and Attenuates MRSA Virulence. / Kaito, Chikara; Saito, Yuki; Ikuo, Mariko; Omae, Yosuke; Mao, Han; Nagano, Gentaro; Fujiyuki, Tomoko; Numata, Shunsuke; Han, Xiao; Obata, Kazuaki; Hasegawa, Setsuo; Yamaguchi, Hiroki; Inokuchi, Koiti; Ito, Teruyo; Hiramatsu, Keiichi; Sekimizu, Kazuhisa.

In: PLoS Pathogens, Vol. 9, No. 4, e1003269, 01.04.2013.

Research output: Contribution to journalArticle

Kaito, C, Saito, Y, Ikuo, M, Omae, Y, Mao, H, Nagano, G, Fujiyuki, T, Numata, S, Han, X, Obata, K, Hasegawa, S, Yamaguchi, H, Inokuchi, K, Ito, T, Hiramatsu, K & Sekimizu, K 2013, 'Mobile Genetic Element SCCmec-encoded psm-mec RNA Suppresses Translation of agrA and Attenuates MRSA Virulence', PLoS Pathogens, vol. 9, no. 4, e1003269. https://doi.org/10.1371/journal.ppat.1003269
Kaito, Chikara ; Saito, Yuki ; Ikuo, Mariko ; Omae, Yosuke ; Mao, Han ; Nagano, Gentaro ; Fujiyuki, Tomoko ; Numata, Shunsuke ; Han, Xiao ; Obata, Kazuaki ; Hasegawa, Setsuo ; Yamaguchi, Hiroki ; Inokuchi, Koiti ; Ito, Teruyo ; Hiramatsu, Keiichi ; Sekimizu, Kazuhisa. / Mobile Genetic Element SCCmec-encoded psm-mec RNA Suppresses Translation of agrA and Attenuates MRSA Virulence. In: PLoS Pathogens. 2013 ; Vol. 9, No. 4.
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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.",
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AU - Mao, Han

AU - Nagano, Gentaro

AU - Fujiyuki, Tomoko

AU - Numata, Shunsuke

AU - Han, Xiao

AU - Obata, Kazuaki

AU - Hasegawa, Setsuo

AU - Yamaguchi, Hiroki

AU - Inokuchi, Koiti

AU - Ito, Teruyo

AU - Hiramatsu, Keiichi

AU - Sekimizu, Kazuhisa

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N2 - 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.

AB - 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.

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