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

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. © 2013 kaito et al.