Alpha-hemolysin of Staphylococcus aureus impairs thrombus formation

Abstract

Toxins are key virulence determinants of pathogens and can impair the function of host immune cells including platelets. Insights into pathogen toxin interference with platelets will be pivotal to improve treatment of patients with bacterial bloodstream infections. In this study, we deciphered the effects of Staphylococcus aureus toxins -hemolysin, LukAB, LukDE and LukSF on human platelets and compared the effects with the pore forming toxin pneumolysin of Streptococcus pneumoniae. In contrast to pneumolysin, -hemolysin initially activates platelets as indicated by CD62P and IIb{beta}3 integrin expression, but the resulting pores also induce alterations in the phenotype of platelets and induce apoptosis of platelets. The presence of small amounts of -hemolysin (0.2 {micro}g/mL) in whole blood abrogates thrombus formation indicating that in systemic infections with S. aureus the stability of formed thrombi is impaired. This might be of high clinical relevance for S. aureus induced endocarditis of the aortic valves. Stabilizing the thrombi by inhibiting -hemolysin induced impairment of platelets likely reduces the risk for septic (micro-)embolization. However, in contrast to pneumolysin, -hemolysin induced platelets damage could not be neutralized by intravenous immune globulins. In contrast to -hemolysin, S. aureus bi-component pore forming leukocidins LukAB, LukED and LukSF do not bind to platelets and had no significant effect on platelet activation and viability. Main point 1: -hemolysin forms pores in platelets, which first activate but then result in apoptosis and impairs thrombus formation and stability Main point 2: Polyvalent immunoglobulins do not neutralize the mode of action of the toxin