Peer Reviewed

1

Document Type

Article

Publication Date

1-2-2008

Keywords

Adhesins, Bacterial, Adult, Blood Platelets, Coagulase, Endocarditis, Bacterial, Fibrinogen, Humans, Immunoglobulin G, Platelet Aggregation, Rheology, Staphylococcus aureus

Comments

This article is available from http://atvb.ahajournals.org/cgi/content/full/28/2/335

Abstract

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. METHODS AND 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.

Disciplines

Life Sciences

Citation

Kerrigan SW, Clarke N, Loughman A, Meade G, Foster TJ, Cox D. Molecular basis for Staphylococcus aureus-mediated platelet aggregate formation under arterial shear in vitro. Arteriosclerosis, Thrombosis, and Vascular Biology 2008;28:335.

PubMed ID

18063809

DOI Link

10.1161/ATVBAHA.107.152058

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Life Sciences Commons

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