Abstract/Summary

Staphylococcus aureus is a major opportunistic pathogenic bacterium which is known to interact with human platelets and modulate their function. Community-Acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) strains are serious human pathogens because of their ability to resist and evade the host immune defences and are commonly resistant to clinically important antibiotics. In the last decade, CA-MRSA infection has become a major worldwide problem and causes a significant increase in the rate of human morbidity and mortality. CA-MRSA can cause acute infections such as sepsis, meningitis and endocarditis due to the production of a class of toxins called phenol-soluble modulins (PSMs) which are considered as important virulence factors. PSM toxins play important roles in the pathogenesis of S. aureus through interaction with immune cells of the host and modulation of their functions. The aims of this study were to determine the effect of S. aureus phenol-soluble modulin α3 (PSMα3) toxin on human platelet activity, what effect S. aureus PSMα3 has on platelet functions and to identify the mechanism of interaction between S. aureus PSMα3 and human platelets. Functional studies showed S. aureus PSMα3 toxin to be an inhibitor of platelet activation. This inhibitory effect of S. aureus PSMα3 was observed with inhibition of platelet aggregation mediated by physiological agonists and S. aureus cells. The toxin caused a reduction in the activation of integrin αIIbβ3 and inhibited spreading and thrombus formation. VPAC1 was identified as the major platelet surface receptor interacting with S. aureus PSMα3. Pre-incubation of platelets with PSMα3 resulted in increased levels of cAMP and consequent activation of protein kinase A (PKA).