Molecular basis for Staphylococcus aureus-mediated platelet aggregate formation under arterial shear in vitro.
OBJECTIVE
Staphylococcus aureus is the most frequent causative organism of infective endocarditis (IE) and is characterized by thrombus formation on a cardiac valve that can embolize to a distant site. Previously, we showed that S. aureus clumping factor A (ClfA) and fibronectin-binding protein A (FnBPA) can stimulate rapid platelet aggregation.


RESULTS
In this study we investigate their relative roles in mediating aggregate formation under physiological shear conditions. Platelets failed to interact with immobilized wild-type S. aureus (Newman) at shear rates <500 s(-1) but rapidly formed an aggregate at shear rates >800 s(-1). Inactivation of the ClfA gene eliminated aggregate formation at any shear rate. Using surrogate hosts that do not interact with platelets bacteria overexpressing ClfA supported rapid aggregate formation under high shear with a similar profile to Newman whereas bacteria overexpressing FnBPA did not. Fibrinogen binding to ClfA was found to be essential for aggregate formation although fibrinogen-coated surfaces only allowed single-platelets to adhere under all shear conditions. Blockade of the platelet immunoglobulin receptor Fc gammaRIIa inhibited aggregate formation.


CONCLUSIONS
Thus, fibrinogen and IgG binding to ClfA is essential for aggregate formation under arterial shear conditions and may explain why S. aureus is the major cause of IE.
Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Steven W
SW
Kerrigan
Niamh
N
Clarke
Anthony
A
Loughman
Gerardene
G
Meade
Timothy J
TJ
Foster
Dermot
D
Cox
D018829:Adhesins, Bacterial / Q000502:physiology; D000328:Adult; D001792:Blood Platelets / Q000382:microbiology* / Q000502:physiology; D003030:Coagulase / Q000502:physiology*; D004697:Endocarditis, Bacterial / Q000503:physiopathology*; D005340:Fibrinogen / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology*; D012212:Rheology; D013211:Staphylococcus aureus / Q000472:pathogenicity*
D018829:Adhesins, Bacterial; C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase; D007074:Immunoglobulin G; C078635:fibronectin-binding proteins, bacterial; D005340:Fibrinogen