Adhesion of Staphylococcus aureus to the vessel wall under flow is mediated by von Willebrand factor-binding protein

Jorien Claes, Thomas Vanassche, Marijke Peetermans, Laurens Liesenborghs, Christophe Vandenbriele, Karen Vanhoorelbeke, Dominique Missiakas, Olaf Schneewind, Marc F Hoylaerts, Ruth Heying, Peter Verhamme

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Abstract

Adhesion of Staphylococcus aureus to blood vessels under shear stress requires von Willebrand factor (VWF). Several bacterial factors have been proposed to interact with VWF, including VWF-binding protein (vWbp), a secreted coagulase that activates the host's prothrombin to generate fibrin. We measured the adhesion of S aureus Newman and a vWbp-deficient mutant (vwb) to VWF, collagen, and activated endothelial cells in a microparallel flow chamber. In vivo adhesion of S aureus was evaluated in the mesenteric circulation of wild-type (WT) and VWF-deficient mice. We found a shear-dependent increase in adhesion of S aureus to the (sub)endothelium that was dependent on interactions between vWbp and the A1-domain of VWF. Adhesion was further enhanced by coagulase-mediated fibrin formation that clustered bacteria and recruited platelets into bacterial microthrombi. In vivo, deficiency of vWbp or VWF as well as inhibition of coagulase activity reduced S aureus adhesion. We conclude that vWbp contributes to vascular adhesion of S aureus through 2 independent mechanisms: shear-mediated binding to VWF and activation of prothrombin to form S aureus-fibrin-platelet aggregates.

Original languageEnglish
JournalBlood
Volume124
Issue number10
Pages (from-to)1669-1676
Number of pages8
ISSN0006-4971
DOIs
Publication statusPublished - 2014

Keywords

  • Animals
  • Bacterial Adhesion/genetics
  • Blood Vessels/metabolism
  • Cells, Cultured
  • Endothelium, Vascular/metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organisms, Genetically Modified
  • Platelet Membrane Glycoproteins/physiology
  • Regional Blood Flow/physiology
  • Staphylococcal Infections/microbiology
  • Staphylococcus aureus/physiology
  • Stress, Mechanical
  • von Willebrand Factor/genetics

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