NHLBI MINORITY SCHOOL FACULTY DEVELOPMENT AWARD

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Infective endocaditis is the most common serious and life-threatening cardiac infection in the United States. The number of cases is expected to increase because of the increasing number of intravenous drug users who are at risk for the development of the disease and the increase in elderly individuals with underlying valvular degenerative changes who also are at risk for the development of the disease. A significant percentage of these cases are caused by members of the viridans streptococci, typically Streptococcus sanguis and Streptococcus mutans. The generally noninvasive S. mutans is a member of the dental caries-causing mutans streptococci and is the most frequent species of the mutans streptococci isolated from the oral cavity of humans. The long-term goal of this study is to broaden the understanding of the pathogenesis of infective endocarditis caused by oral streptococci. The goal of this project is to identify and characterize the bacterial cell surface molecules that are involved in the adherence of mutans streptococci to heart tissue. The specific aims of this project are: 1) to characterize the binding and adherence of S. mutans cells to extracellular matrix; 2) to construct S. mutans mutant strains using transposon mutagenesis with defects in their ability to bind fibronectin; 3) to evaluate the role of fibronectin-binding by S. mutans in infective endocarditis by determining in a model of experimental endocarditis the virulence of fibronectin-binding-defective mutant strains; 4) to compare the extracellular and cell membrane proteins of normal fibronectin-binding S. mutans cells and fibronectin-binding-defective S. mutans cells and 5) to clone and characterize the gene encoding the fibronectin-binding receptor on the surface of S. mutans cells.