Staphylococcus aureus adhesion via Spa, ClfA, and SdrCDE to immobilized platelets demonstrates shear-dependent behavior.
OBJECTIVE
The objective of this study is to delineate the molecular mechanisms responsible for Staphylococcus aureus-platelet adhesion as a function of physiologically relevant wall shear stresses.


RESULTS
A parallel plate flow chamber was used to quantify adhesion of wild-type, Spa-, ClfA- and SdrCDE- strains to immobilized platelet layers. In the absence of plasma, adhesion increases with increasing wall shear rate from 100 to 5000 seconds(-1). The presence of plasma significantly enhances adhesion at all shear levels. Addition of exogenous fibrinogen yields adhesion levels similar to plasma in the lower shear regimes, but has a diminishing effect on potentiating adhesion at higher shear rates. Alternatively, as shear rate increases von Willebrand factor (VWF) plays an increasingly significant role in mediating binding.


CONCLUSIONS
Addition of plasma proteins potentiates S aureus-platelet interactions at all shear rates examined. Whereas fibrinogen plays a significant role in all shear regimes, VWF mediation becomes increasingly important as wall shear rate increases. Fibrinogen binding is dependent on bacterial adhesins ClfA and SdrCDE whereas Spa is the dominant receptor for VWF.
George
Niraj Procopio Evagrio
NP
Department of Chemical and Biochemical Engineering, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Wei
Qi
Q
Shin
Pyong Kyun
PK
Konstantopoulos
Konstantinos
K
Ross
Julia M
JM
D018829:Adhesins, Bacterial / Q000502:physiology*; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects / Q000502:physiology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001798:Blood Proteins / Q000502:physiology; D005340:Fibrinogen / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000145:classification / Q000502:physiology*; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000502:physiology
D018829:Adhesins, Bacterial; D001798:Blood Proteins; D009842:Oligopeptides; D010080:Oxazoles; D010975:Platelet Aggregation Inhibitors; C116340:XV 454; D014841:von Willebrand Factor; D005340:Fibrinogen; C046617:arginyl-glycyl-aspartyl-serine; D000409:Alanine