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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL030069-07
Application #
3341134
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1982-08-01
Project End
1991-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Dougherty, B A; van de Rijn, I (1994) Molecular characterization of hasA from an operon required for hyaluronic acid synthesis in group A streptococci. J Biol Chem 269:169-75
Tart, R C; van de Rijn, I (1993) Identification of the surface component of Streptococcus defectivus that mediates extracellular matrix adherence. Infect Immun 61:4994-5000
Sieling, P A; Thomas, M J; van de Rijn, I (1992) Characterization of the Streptococcus adjacens group antigen structure. J Bacteriol 174:349-54
Sieling, P A; van de Rijn, I (1991) Evaluation of the immune response in protection against experimental Streptococcus defectivus endocarditis. J Lab Clin Med 117:402-9
Tagg, J R; van de Rijn, I (1991) Inverse correlation in nutritionally variant streptococci between the production of bacteriolytic activity and sensitivity to a Streptococcus pyogenes bacteriocinlike inhibitory substance. J Clin Microbiol 29:848-9
Tart, R C; van de Rijn, I (1991) Analysis of adherence of Streptococcus defectivus and endocarditis-associated streptococci to extracellular matrix. Infect Immun 59:857-62
Sieling, P A; van de Rijn, I (1991) Purification and characterization of Streptococcus adjacens (nutritionally variant Streptococcus serotype II) group antigen. Infect Immun 59:592-9
van de Rijn, I (1988) Analysis of cross-protection between serotypes and passively transferred immune globulin in experimental nutritionally variant streptococcal endocarditis. Infect Immun 56:117-21
George, M; van de Rijn, I (1988) Purification of serotype I antigen from nutritionally variant streptococci. Infect Immun 56:1222-31
George, M; van de Rijn, I (1988) Nutritionally variant streptococcal serotype I antigen. Characterization as a lipid-substituted poly(ribitol phosphate). J Immunol 140:2008-15

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