Staphylococcus aureus is one of the most successful human pathogens, asymptomatically colonizing over 2 billion individuals worldwide and capable of causing invasive and deadly opportunistic infections. We are using genomic approaches to identify virulence determinants associated with S. aureus infections and determine their roles in pathogenicity. The numerous putative virulence factors we have identified include toxins, bacterial surface proteins that mediate adhesion to host tissue as well as putative regulatory elements and genes with possible roles in evasion of innate immunity. We are currently using in vivo and in vitro experimental approaches to verify the functions of these genes. In addition, we have recently initiated a systems biology approach employing animal infection models, deep genome sequencing and RNAseq transcriptome analysis to identify the genomic and transcriptional basis of chronic and complicated S. aureus infections. In addition to Staphylococcus aureus, the Staphylococcal family includes several species which are emerging as pathogens of clinical relevance. We are currently working on Staphylococcus epidermidis and the contribution of vertical and horizontal genome evolution to their increased virulence. In S. epidermidis, we have identified a putative pathogenicity island (SePI), which appears to have been acquired by cross-species mobilization from S. aureus. We are attempting to determine the mobilization mechanism of the SePI and its role in virulence.
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