title: Shear-Resistant Binding to von Willebrand Factor Allows Staphylococcus lugdunensis to Adhere to the Cardiac Valves and Initiate Endocarditis.
abstract: BACKGROUND
  Staphylococcus lugdunensis is an emerging cause of endocarditis. To cause endovascular infections, S. lugdunensis requires mechanisms to overcome shear stress. We investigated whether platelets and von Willebrand factor (VWF) mediate bacterial adhesion to the vessel wall and the cardiac valves under flow.
  
  
  METHODS
  S. lugdunensis binding to VWF, collagen, and endothelial cells was studied in a parallel flow chamber in the absence and presence of platelets. In vivo adhesion of S. lugdunensis was evaluated in a mouse microvasculature perfusion model and a new mouse model of endocarditis.
  
  
  RESULTS
  Contrary to other coagulase-negative staphylococci, S. lugdunensis bound to VWF under flow, thus enabling its adhesion to endothelial cells and to the subendothelial matrix. In inflamed vessels of the mesenteric circulation, VWF recruited S. lugdunensis to the vessel wall. In a novel endocarditis mouse model, local inflammation and the resulting release of VWF enabled S. lugdunensis to bind and colonize the heart valves.
  
  
  CONCLUSIONS
  S. lugdunensis binds directly to VWF, which proved to be vital for withstanding shear forces and for its adhesion to the vessel wall and cardiac valves. This mechanism explains why S. lugdunensis causes more-aggressive infections, including endocarditis, compared with other coagulase-negative staphylococci.
authors.affiliation: Center for Molecular and Vascular Biology, KU Leuven, Belgium.
authors.forename: Laurens
authors.initials: L
authors.lastname: Liesenborghs
authors.affiliation: Center for Molecular and Vascular Biology, KU Leuven, Belgium.
authors.forename: Marijke
authors.initials: M
authors.lastname: Peetermans
authors.affiliation: Center for Molecular and Vascular Biology, KU Leuven, Belgium.
authors.forename: Jorien
authors.initials: J
authors.lastname: Claes
authors.affiliation: Center for Molecular and Vascular Biology, KU Leuven, Belgium.
authors.forename: Tiago Rafael
authors.initials: TR
authors.lastname: Veloso
authors.affiliation: Center for Molecular and Vascular Biology, KU Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Vandenbriele
authors.affiliation: Center for Molecular and Vascular Biology, KU Leuven, Belgium.
authors.forename: Maarten
authors.initials: M
authors.lastname: Criel
authors.affiliation: Center for Molecular and Vascular Biology, KU Leuven, Belgium.
authors.forename: Marleen
authors.initials: M
authors.lastname: Lox
authors.affiliation: Department of Internal Medicine, KU Leuven, Belgium.
authors.forename: Willy E
authors.initials: WE
authors.lastname: Peetermans
authors.affiliation: Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Heilbronner
authors.affiliation: Laboratory of Clinical Chemistry and Haematology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.affiliation: Center for Molecular and Vascular Biology, KU Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vanassche
authors.affiliation: Center for Molecular and Vascular Biology, KU Leuven, Belgium.
authors.forename: Marc F
authors.initials: MF
authors.lastname: Hoylaerts
authors.affiliation: Center for Molecular and Vascular Biology, KU Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Verhamme
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology*; D004697:Endocarditis, Bacterial / Q000382:microbiology*; D005786:Gene Expression Regulation; D006351:Heart Valves / Q000382:microbiology*; D006801:Humans; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D033081:Shear Strength; D013203:Staphylococcal Infections / Q000382:microbiology*; D057787:Staphylococcus lugdunensis / Q000502:physiology*; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D014841:von Willebrand Factor
keywords: Staphylococcus lugdunensis; endocarditis; endothelial cells; platelets; shear stress; von Willebrand factor