Mechanisms of platelet aggregation by viridans group streptococci

Abstract

The direct aggregation of platelets is thought to be an important event in the pathogenesis of viridans streptococcal endocarditis, but the mechanisms for platelet activation are unknown. We evaluated the processes by which two endocarditis-producing strains of viridans group streptococci activated human platelets in vitro, as measured by platelet cyclooxygenase activity, secretion, and aggregation. Addition of either streptococcal strain to platelets suspended in whole plasma resulted in a mean lag phase of 15.3 min, followed by platelet secretion and brisk aggregation. The lag phase duration was dependent on the platelet donor and appeared to be a function of direct platelet-bacterial interaction. Aggregation was partially inhibited by 20 M indomethacin and blocked completely by 1 mg of apyrase, an extracellular ADP hydrolase, per ml. Neither strain aggregated washed platelets suspended in Tyrode solution alone. However, both strains produced maximal aggregation when the platelet suspension was supplemented with 10% (final concentration) normal plasma. Studies with factor-deficient plasmas demonstrated that exogenous fibrinogen was required for aggregation. One or more additional plasma components were needed, which eluted with a molecular weight of 67,000 to 130,000 on gel permeation chromatography. These cofactors have not been described for other platelet agonists, which suggests that viridans streptococci may aggregate human platelets by a novel mechanism.

Evidence for the involvement of complement proteins in platelet aggregation by Streptococcus sanguis NCTC 7863

“…Furthermore, a 150 kD protein, which possesses a 'collagen-like' domain, has been isolated from a strain of S. sanguis Erickson et al, 1992), and appears to interact with a 175 kD protein, possibly complexed with the main collagen receptor on the platelet membrane, glycoprotein Ia (GPIa) (Gong et al, 1995). As well as this, we have previously shown the involvement of at least two other membrane receptors, GPIb and GPIIb/IIIa (the integrin platelets to bacteria (Ford et al, 1993;Herzberg et al, 1983a;Sullam et al, 1987). Washed platelets are not aggregated by S. sanguis (Ford et al, 1993).…”

“…Oral streptococci are the most common causative agents of IE and among these Streptococcus sanguis and S. oralis are the most frequent . There have been several reports that S. sanguis can directly aggregate platelets in vitro (Douglas et al, 1990;Herzberg et al, 1983a;Manning et al, 1994;Sullam et al, 1987) but the mechanisms by which this occurs are not entirely clear. Previous work has shown that (i) there is a lag between the addition of bacteria and the onset of aggregation, the period of which varies between subjects (Ford et al, 1993;Herzberg et al, 1990), (ii) platelets must be functional (Ford et al, 1993;Herzberg et al, 1983a), and (iii) that bacterial interaction with platelets results in true aggregation accompanied by secretion of granule contents (Ford et al, 1993;Herzberg et al, 1983a).…”

Biological roles of glycans

“…Of course commensals may take advantage of such mucin binding to remain within their preferred ecological niche (797)(798)(799)(800) and to favor dental biofilm development (801). But on the rare occasions when such bacteria accidentally find their way into the bloodstream, these same commensalism-favoring adhesins become virulence factors, mediating interactions with platelets, which act as carriers of the organisms to eventual infection of damaged heart valves (798,(802)(803)(804)(805)(806)(807). This is a recurring theme at sites of interspecies interactions, wherein factors favoring routine commensalism turn into potent "virulence factors", on the occasions when physical barriers are breached and/or host immunity is compromised.…”

Platelet Aggregation by Strains of Enterococci

“…Among microorganisms possessing the ability to induce platelet aggregation in PRP, Gram-positive cocci, S. aureus, S. sanguis, and group A streptococci have been studied in detail (8,18,24,28,35,36,39,43). Concerning the interaction between enterococci and platelets, more detailed investigations have been needed for comparison with other bacteria-platelets interaction, although Clawson et al (8) reported some properties of the platelet aggregation.…”

“…The mechanisms of platelet aggregation by these stimuli have been studied in detail (16). In contrast to these effects favorable for hemostasis, platelets also possess a pathogenic significance in disseminated intravascular coagulation (DI C) during sepsis or infective endocarditis (3,7,22,30) and observations have been made concerning the relationship between the platelet and several species of microorganisms, Staphylococcus aureus (8,18,28,40), coagulasenegative staphylococci (CNS) (41), streptococci (24,35,36,39,43), Listeria monocytogenes (9), Fusobacterium necrophorum (15), Aspergillus fumigatus (31), Candida albicans (33), Histoplasma capsulatum (10).…”