Evidence of latent molecular diversity determining the virulence of community-associated MRSA USA300 clones in mice.

INTRODUCTION: The USA300 clone of community-associated MRSA is reported to be hypervirulent and epidemic in the United States. This clone causes a variety of diseases from lethal pneumonia to mild skin infections. We hypothesized that evolutionary diversity may exist among USA300 clones, which may link virulence traits with host responses and mortality rates. METHODS: USA300 isolates from severe pneumonia (IP) and skin infection (IS) were characterized by pulsed-field gel electrophoresis (PFGE) and next-generation sequencing. Their virulence traits and host responses were compared in a lung infection model. RESULTS: The two USA300 isolates were found to be identical in genomic analysis. Robust IL-6 production, aggregation of bacteria, and hemorrhaging were observed in IP-infected lungs, which were associated with a higher rate of mortality than that observed with strain IS. Few neutrophils were detected in the lungs infected with strain IP, even at high bacterial loads. Massive production of α-toxin and coagulase were evident during the early phase of IP infection, and robust gene expression of hla (α-toxin) and lukS-PV (Panton-Valentine leukocidin), but not coa, agrA, or rnaIII, was confirmed in vitro. Strain IP also induced strong hemolysis in red blood cells. CONCLUSIONS: The present data demonstrated latent diversity in the virulence of USA300 clones. Unknown regulatory mechanisms, probably involving a host factor(s) as a trigger, may govern the virulence expression and resultant high mortality in certain sub-clones of USA300.