Infective endocarditis is still an important disease that accounts for 0.3-3.0/1000 of all hospital admissions and the viridans streptococci remain the most frequent cause of subacute bacterial endocarditis. In this group of streptococci, the nutritionally variant streptococci account for 6-7% of the disease in man. To date, this is the first comprehensive analysis of the surface components of these strains. The overall objective of this research proposal is to continue a systematic study of the surface components of the nutritionally variant streptococci (NVS) in order to better understand the interaction of these bacteria with the heart valves in infective subacute bacterial endocarditis. Toward this objective we plan to determine the identity of the antigen(s) responsible for protection using the rabbit endocarditis model. The remaining surface components still to be analyzed in serotype I organisms for this function are the cell wall protein and ribitol teichoic acid. In addition we will characterize our present set of monoclonal antibodies against serotype I components. Produce further monoclonals against the serotype-specific antigens and the molecule(s) involved in adherence and/or colonization from serotype II and III organisms. Furthermore the identity of the antigen(s) responsible for protection using the rabbit endocarditis model for strains from serotypes II and III will be determined. Next, the NVS serotype II and III antigens if different from the respective protective antigens will be isolated and characterized. Finally, the analysis of antibody present in patients with NVS endocarditis will continue. The knowledge gained from the proposed studies will permit investigators to study the interaction between the surface of the NVS and the cardiac valves. In addition, it continues to lay the ground work for the rapid identification of these organisms upon isolation from blood culture. Finally, completion of these specific aims possibly could lead to a vaccine which would be effective in the population at high risk to this disease. Infective endocarditis is a serious disease in that if not created rapidly, secondary complications arise including renal and neurological damage. However 60% of the deaths caused by this disease is due to congestive heart failure. The NVS are important in that patients with endocarditis caused by these organisms have high rates of antimicrobial failure, relapse, and fatality.
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