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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 SCC mec  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.

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