Potential Role of a Bacteriophage Encoded Amidase in Staphylococcus aureus Associated Infective Endocarditis

Staphylococcus aureus is a commensal bacterium that causes a wide range of clinical outcomes, from skin and soft tissue infections, to severe invasive infections. This bacterium is a clonal species with multiple genotypes that are hypothesized to be associated with different clinical disease outcomes. This is supported by the recent observation that two S. aureus clonal complexes (5 and 30) are associated with hematogenous complications, such as osteomyelitis and endocarditis. In previous work using array comparative genome hybridization, we identified 14 genes common in these invasive strains not previously implicated in virulence.  Many of these genes were bacteriophage encoded, two of which encode an N-acetylmuramyl-L-alanine amidase. Recent data showing a Streptococcus mitis paralog of the S. aureus amidases mediated binding to platelets led us to ask if they shared this function. Platelets play an important role in the pathogenesis of infective endocarditis by providing an adhesive site for bacteria to bind on damaged heart valves. Preliminary data shows that the S. aureus amidase can bind to human platelets as assessed by an enzyme-linked immunosorbent assay. Additional assays such as flow cytometry will be performed to further probe if this interaction is a direct or indirect interaction and if this adherence plays any role in platelet activation. Staphylococcus aureus is the leading cause of infective endocarditis and increasing in antimicrobial resistance. Information we gain from our research may enhance our understanding of the host-bacterial interactions in the pathogenesis of this disease and may contribute to the search for new therapeutic targets.