In FY 2014, we continued investigation of the staphylococcal peptide cytolysins, phenol-soluble modulins (PSMs). Current efforts focus on structure-function relationship studies of PSMs, antimicrobial activities of PSMs, and the PSM exporter, with the long-term goals to produce anti-PSM therapeutics for the treatment of staphylococcal infections. We have identified the PSM exporter and are currently setting up translational follow-up projects to find drugs interfering with PSM export. Furthermore, we analyzed the basis of virulence in a global community-assocoiated MRSA strain (ST72 from Korea), which does not harbor the genes encoding the Panton-Valentine leukocidin. Finally, we found that the production of a specific allelic variant of the most cytolytic and pro-inflammatory PSM, PSM alpha , is linked to an MRSA lineage that is a frequent cause of sepsis.
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