Platelet-streptococcal interactions in endocarditis.
Infective endocarditis is characterized by the formation of septic masses of platelets on the surfaces of heart valves and is most commonly caused by viridans streptococci. Streptococcal virulence in endocarditis involves factors that promote infectivity and pathogenicity. Adhesins and exopolysaccharide (glycocalyx) contribute to infectivity. Although many factors may contribute to pathogenicity, the platelet aggregation-associated protein (PAAP) of Streptococcus sanguis contributes directly to the development of experimental endocarditis. PAAP is synthesized as a rhamnose-rich glycoprotein of 115 kDa and contains a collagen-like platelet-interactive domain, pro-gly-glu-gln-gly-pro-lys. Expressed on the cell wall of platelet aggregation-inducing strains (Agg+) of S. sanguis, PAAP apparently interacts with a signal-transducing receptor complex on platelets, which includes a novel 175-kDa alpha 2-integrin-associated protein and a 65-kDa collagen-binding component. From available data, the role of PAAP in the pathogenesis of experimental endocarditis may be explained by a proposed mechanistic model. On injured heart valves, PAAP first enhances platelet accumulation into a fibrin-enmeshed thrombus (vegetation), within which S. sanguis colonizes. Colonizing bacteria must resist platelet microbicidal protein (PMPR). The aggregation of platelets on the heart valve may be potentiated by an ectoATPase expressed on the surface of the S. sanguis and platelet alpha-adrenoreceptors that respond to endogenous catecholamines. The expression of PAAP may be modified during infection. Collagen is exposed on damaged heart valves; fever (heat shock) occurs during endocarditis. In response to heat shock or collagen in vitro, PAAP expression is altered. After colonization, streptococcal exotoxin(s) may cause fever. Proteases and other enzymes from streptococci and host sources may directly destroy the heart valves. When PAAP is unexpressed or neutralized with specific antibodies, experimental endocarditis runs a milder course and vegetations are smaller. The data suggest strongly, therefore, that the role of PAAP may overlap the colonization function of putative adhesins such as FimA or SsaB. Finally, PAAP also contributes to the development of the characteristic septic mural thrombus (vegetation) of infective endocarditis and the signs of valvular pathology.
Department of Preventive Sciences, School of Dentistry, University of Minnesota, Minneopolis 55455, USA.
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Herzberg
D000251:Adenosine Triphosphatases / Q000235:genetics; D018829:Adhesins, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001427:Bacterial Toxins / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D001798:Blood Proteins / Q000502:physiology; D018925:Chemokines; D003094:Collagen / Q000502:physiology; D004697:Endocarditis, Bacterial / Q000473:pathology* / Q000503:physiopathology; D005337:Fibrin / Q000502:physiology; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000502:physiology; D006351:Heart Valves / Q000382:microbiology; D006801:Humans; D016023:Integrins / Q000502:physiology; D010974:Platelet Aggregation; D011135:Polysaccharides, Bacterial / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D012210:Rhamnose / Q000502:physiology; D015398:Signal Transduction; D013290:Streptococcal Infections / Q000473:pathology* / Q000503:physiopathology; D013291:Streptococcus / Q000472:pathogenicity / Q000502:physiology*; D013298:Streptococcus sanguis / Q000235:genetics / Q000502:physiology; D014774:Virulence; D001620:beta-Thromboglobulin
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001798:Blood Proteins; D018925:Chemokines; D006023:Glycoproteins; D016023:Integrins; C061615:PPBP protein, human; D011135:Polysaccharides, Bacterial; D011942:Receptors, Adrenergic, alpha; D001620:beta-Thromboglobulin; D005337:Fibrin; D003094:Collagen; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D012210:Rhamnose