Streptococcal genomics and pathogenesis

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DESCRIPTION (provided by applicant): Viridans streptococci are the leading cause of infective endocarditis, a serious illness which affects about 22,000 people per year in the US and kills over 2,000. These bacteria are also common agents of bacteremia, especially in neutropenic patients. Identification of streptococcal virulence factors would lead to a better understanding of the pathogenesis of streptococcal bacteremia and endocarditis and to the identification of targets for prevention and therapy. Dr. Todd Kitten is currently applying signature-tagged mutagenesis to identify Streptococcus sanguis virulence factors for endocarditis. This approach requires no prior assumptions concerning the importance of any particular gene or activity in disease causation. Instead, it relies on the infection process in an animal model to identify the bacterial genes needed for disease and their relative contributions. The proposed career development project will extend this work by providing Dr. Kitten with the bioinformatic skills necessary to perform sophisticated analyses of genes and pathways identified by signature tagging as required for virulence. The imminent completion at Virginia Commonwealth University of new, dedicated bioinformatic facilities, bioinformatic curricula, and the S. sanguis genome sequence have combined to create the perfect opportunity for Dr. Kitten to obtain and hone these skills. Of equal importance, Dr. Kitten will dramatically extend his expertise, perspective, and research material by engaging in infectious disease training activities and by obtaining clinical data and strains from patients infected with viridans streptococci. These activities will leverage the world-class teaching hospital and clinical researchers available at VCU. The clinical experience, data and strains will ensure that Dr. Kitten's research remains directed toward pressing and pragmatic clinical pursuits, while the bioinformatic training will ensure that he has the skills necessary to apply the latest and most suitable approaches to these pursuits.