Effects of Suilysin on Streptococcus suis-Induced Platelet Aggregation

Abstract

Blood platelets play important roles during pathological thrombocytopenia in streptococcal toxic shock syndrome (STSS). <i>Streptococcus suis</i> (<i>S. suis</i>) an emerging human pathogen, can cause STSS similarly to <i>S. pyogenes</i>. However, <i>S. suis</i> interactions with platelets are poorly understood. Here, we found that suilysin (SLY), different from other bacterial cholesterol-dependent cytolysins (CDCs), was the sole stimulus that induced platelet aggregation. Furthermore, the inside-out activation of GPIIb/IIIa of platelets mediated SLY-induced platelet aggregation. This process was triggered by Ca²⁺ influx that depend on the pore forming on platelets by SLY. Additionally, although SLY induced α-granule release occurred via the MLCK-dependent pathway, PLC-β-IP3/DAG-MLCK and Rho-ROCK-MLCK signaling were not involved in SLY-induced platelet aggregation. Interestingly, the pore dependent Ca²⁺ influx was also found to participate in the induction of platelet aggregation with pneumolysin (PLY) and streptolysin O (SLO), two other CDCs. It is possible that the CDC-mediated platelet aggregation we observed in <i>S. suis</i> is a similar response mechanism to that used by a wide range of bacteria. These findings might lead to the discovery of potential therapeutic targets for <i>S. suis</i>-associated STSS.