title: Adhesion of Staphylococcus aureus to the vessel wall under flow is mediated by von Willebrand factor-binding protein.
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.
authors.affiliation: Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, and.
authors.forename: Jorien
authors.initials: J
authors.lastname: Claes
authors.affiliation: Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vanassche
authors.affiliation: Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, and.
authors.forename: Marijke
authors.initials: M
authors.lastname: Peetermans
authors.affiliation: Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, and.
authors.forename: Laurens
authors.initials: L
authors.lastname: Liesenborghs
authors.affiliation: Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, and.
authors.forename: Christophe
authors.initials: C
authors.lastname: Vandenbriele
authors.affiliation: Laboratory for Thrombosis Research, Interdisciplinary Research Facility Life Sciences, Kulak, Katholieke Universiteit Leuven, Leuven, Belgium;
authors.forename: Karen
authors.initials: K
authors.lastname: Vanhoorelbeke
authors.affiliation: Department of Microbiology, University of Chicago, IL; and.
authors.forename: Dominique
authors.initials: D
authors.lastname: Missiakas
authors.affiliation: Department of Microbiology, University of Chicago, IL; and.
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
authors.affiliation: Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, and.
authors.forename: Marc F
authors.initials: MF
authors.lastname: Hoylaerts
authors.affiliation: Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, and Cardiovascular Developmental Biology, Department of Cardiovascular Sciences, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Ruth
authors.initials: R
authors.lastname: Heying
authors.affiliation: Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, and.
authors.forename: Peter
authors.initials: P
authors.lastname: Verhamme
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics*; D001808:Blood Vessels / Q000378:metabolism / Q000382:microbiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism / Q000382:microbiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D030781:Organisms, Genetically Modified; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology*; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000502:physiology*; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; C028254:von Willebrand factor receptor