Staphylococcus aureus adhesion via Spa, ClfA, and SdrCDE to immobilized platelets demonstrates shear-dependent behavior

Arterioscler Thromb Vasc Biol. 2006 Oct;26(10):2394-400. doi: 10.1161/01.ATV.0000237606.90253.94. Epub 2006 Jul 20.

Abstract

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.

Methods and 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adhesins, Bacterial / physiology*
  • Alanine / analogs & derivatives
  • Alanine / pharmacology
  • Bacterial Adhesion / drug effects
  • Bacterial Adhesion / physiology*
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Blood Proteins / physiology
  • Fibrinogen / metabolism
  • Fibrinogen / physiology
  • Humans
  • Oligopeptides / pharmacology
  • Oxazoles / pharmacology
  • Platelet Adhesiveness / drug effects
  • Platelet Adhesiveness / physiology*
  • Platelet Aggregation Inhibitors / pharmacology
  • Staphylococcus aureus / classification
  • Staphylococcus aureus / physiology*
  • Stress, Mechanical
  • von Willebrand Factor / physiology

Substances

  • Adhesins, Bacterial
  • Blood Proteins
  • Oligopeptides
  • Oxazoles
  • Platelet Aggregation Inhibitors
  • XV 454
  • von Willebrand Factor
  • Fibrinogen
  • arginyl-glycyl-aspartyl-serine
  • Alanine