Certain streptococci isolated from dental plaque (or blood) bind and activate (shape change reaction, granule release) human platelets, which then aggregate into a septic thrombus. These interactions mimic in vitro the formation of the intracardiac vegetations characteristic of subacute bacterial endocarditis (SBE), a systemic complication associated with dental care. The definable platelet resonse end points of binding, activation and aggregation also provide a unique model to explore the molecular basis of interaction between the various surface components of oral streptococci and other essentially passive, mammalian cells and tissues. During years 04-06, class I, II and III components of S. sanguis (a prototypic SBE microorganism originating in dental plaque) implicated (years 01-03) in the sequence of binding, activation aggregation of platelets, will be purified and characterized. Biochemical purification will combine conventional column chromatography with high performance liquid chromatography. Purification using immunoaffinity techniques will employ existing polyclonal and new monoclonal antibody reagents. Since platelet interactions with solubilized components differ from that seen with native components, development of monoclonal antibodies to native, exposed surface epitopes on S. sanguis will identify and distinguish interacting components associated with the ascribed platelet responses prior to their extraction or fractionation. Characterization will include chemical, physical and immunological criteria of purity, chemical composition and key structural features, correspondence of function-associated antigen with a macromolecular component(s), localization of functional antigens in situ (on wall of S. sanguis) and determination of the number and affinity of platelet binding or interaction sites for the purified S. sanquis components. These data will refine the in vitro model for platelet-streptococcal interactions. Understanding the molecular basis of these interactions may pinpoint new strategies for prevention, diagnosis and treatment of SBE and related oral streptococcal infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE005501-06
Application #
3219465
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
1980-08-01
Project End
1987-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Herzberg, Mark C; Nobbs, Angela; Tao, Lin et al. (2005) Oral streptococci and cardiovascular disease: searching for the platelet aggregation-associated protein gene and mechanisms of Streptococcus sanguis-induced thrombosis. J Periodontol 76:2101-5
Herzberg, M C (2001) Coagulation and thrombosis in cardiovascular disease: plausible contributions of infectious agents. Ann Periodontol 6:16-9
Herzberg, M C; Weyer, M W (1998) Dental plaque, platelets, and cardiovascular diseases. Ann Periodontol 3:151-60
Meyer, M W; Gong, K; Herzberg, M C (1998) Streptococcus sanguis-induced platelet clotting in rabbits and hemodynamic and cardiopulmonary consequences. Infect Immun 66:5906-14
Herzberg, M C; Meyer, M W; Kilic, A et al. (1997) Host-pathogen interactions in bacterial endocarditis: streptococcal virulence in the host. Adv Dent Res 11:69-74
Herzberg, M C; Meyer, M W (1996) Effects of oral flora on platelets: possible consequences in cardiovascular disease. J Periodontol 67:1138-42
Herzberg, M C (1996) Platelet-streptococcal interactions in endocarditis. Crit Rev Oral Biol Med 7:222-36
Erickson, P R; Herzberg, M C (1995) Altered expression of the platelet aggregation-associated protein from Streptococcus sanguis after growth in the presence of collagen. Infect Immun 63:1084-8
Erickson, P R; Herzberg, M C (1993) Evidence for the covalent linkage of carbohydrate polymers to a glycoprotein from Streptococcus sanguis. J Biol Chem 268:23780-3
Erickson, P R; Herzberg, M C (1993) The Streptococcus sanguis platelet aggregation-associated protein. Identification and characterization of the minimal platelet-interactive domain. J Biol Chem 268:1646-9