Blockade of glycoprotein IIb/IIIa by crotavirin, a member of disintegrins, prevents platelet from activation and aggregation by Staphylococcus aureus bacteria.
Interaction with circulating platelets is considered an important virulent mechanism for Staphylococcus aureus (S. aureus) bacteria to induce endocarditis, a severe infectious disease with high incidence of systemic thrombosis. It therefore represents an important target for pharmacological intervention. In this study, we found that the clinical isolate S. aureus 30326 induced activation and aggregation of washed human platelets in a fibrinogen-dependent manner and this platelet reactivity was abrogated by crotavirin, a snake venom-derived glycoprotein (GP) IIb/IIIa antagonist, indicating that crotavirin is able to protect platelets from activation and aggregation by S. aureus 30326. When tested at a concentration that prevented the platelet reactivity of S. aureus 30326, crotavirin also interfered with the binding of bacteria to washed human platelets supplemented with fibrinogen. The fibrinogen-binding activity of S. aureus has been shown to be essential for S. aureus to trigger platelet activation and aggregation. Crotavirin failed to affect the fibrinogen binding of S. aureus 30326 and neither did it bind to this microbe, suggesting that the inhibitory action of crotavirin on the S. aureus 30326-platelet interaction resulted from the occupation of platelet GPIIb/IIIa. Taken together, these results demonstrate an important role for GPIIb/IIIa in mediating the interaction of platelets with S. aureus in the presence of fibrinogen and platelet GPIIb/IIIa thus appears to be a new target for the intervention of S. aureus-platelet interaction.
Liu
Chao-Zong
CZ
Department of Pharmacology, College of Medicine, Tzu Chi University, Hualien City, Hualien 970, Taiwan. czliu33@mail.tcu.edu.tw
Huang
Hsin-Yi
HY
Tsai
Pei-Jane
PJ
Shih
Mei-Hsu
MH
D001422:Bacterial Adhesion; D001792:Blood Platelets / Q000382:microbiology* / Q000502:physiology; D019483:Disintegrins; D005340:Fibrinogen; D006801:Humans; D010455:Peptides / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000502:physiology; D013211:Staphylococcus aureus / Q000472:pathogenicity*
D019483:Disintegrins; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C098620:crotavirin; D005340:Fibrinogen