Mobile Genetic Element SCCmec-encoded psm-mec RNA Suppresses Translation of agrA and Attenuates MRSA Virulence: e1003269

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 kn...

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Bibliographic Details
Published in:PLoS pathogens 2013-04, Vol.9 (4)
Main Authors: 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
Format: Article
Language:English
Subjects:
Experiments
Genes
Genomes
Health sciences
Microbiology
Standard deviation
Staphylococcus aureus
Staphylococcus infections
Toxins
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Summary: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.
ISSN:1553-7366
1553-7374
DOI:10.1371/journal.ppat.1003269