Background: Streptococcus pneumoniae (pneumococcus) is a commensal of the upper respiratory tract but also causative agent of severe diseases like community acquired pneumonia associated acute respiratory distress syndrome (ARDS), meningitis and sepsis. During dissemination via the blood stream, pneumococci associate with platelets. Platelets are an important diagnostic marker in pneumococcus infections, because low platelet counts correlate with high mortality rates. A major virulence factor of pneumococci is the pore-forming toxin pneumolysin (Ply). This cholesterol-dependent cytolysin has earlier been reported to activate platelets as indicated by high CD62P surface expression.

Aims: To investigate the impact of pneumococcal Ply on platelet activation and function.

Methods: Platelets were isolated from healthy volunteers. The impact of Ply on activation and function of platelets was assessed by measuring CD62P and PAC-1 binding, platelet aggregation, release of intracellular Ca²⁺, and platelet viability. The effect of Ply on platelet adhesion to collagen and thrombus formation was measured in a flow chamber.

Results: Ply mediated pore formation in platelets (Fig.1A) occurred in a concentration dependent manner and was associated with Ca²⁺-release (Fig. 1B) and loss of platelet viability. Ply did not activate platelets as indicated by unaltered PAC-1 binding. Platelets aggregated in response to agonists only at sublytic Ply concentrations. Increased levels of CD62P was due to pore formation and intracellular CD62P staining. Consistent with Ply induced platelet lysis, thrombus formation in whole blood was reduced by Ply treatment in a concentration dependent manner (Fig. 1C).

Conclusions: Pneumococcal Ply perforates platelet membranes, which leads to loss of platelet viability and function. The severe impact of Ply on platelet function and viability suggests that Ply contributes to capillary leakage during severe cases of pneumococcal pneumonia associated ARDS.

Funded by: Project number 374031971 – TRR 240.

« Back to ISTH 2020 Congress

ISTH Congress Abstracts - https://abstracts.isth.org/abstract/streptococcus-pneumoniae-toxin-pneumolysin-renders-platelets-non-functional/