Shear-Resistant Binding to von Willebrand Factor Allows Staphylococcus lugdunensis to Adhere to the Cardiac Valves and Initiate Endocarditis

Laurens Liesenborghs, Marijke Peetermans, Jorien Claes, Tiago Rafael Veloso, Christophe Vandenbriele, Maarten Criel, Marleen Lox, Willy E Peetermans, Simon Heilbronner, Philip G de Groot, Thomas Vanassche, Marc F Hoylaerts, Peter Verhamme

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalJournal of Infectious Diseases
Volume213
Issue number7
Pages (from-to)1148-56
Number of pages9
ISSN0022-1899
DOIs
Publication statusPublished - 1-Apr-2016

Keywords

  • Animals
  • Bacterial Adhesion/physiology
  • Endocarditis, Bacterial/microbiology
  • Gene Expression Regulation
  • Heart Valves/microbiology
  • Humans
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Binding
  • Shear Strength
  • Staphylococcal Infections/microbiology
  • Staphylococcus lugdunensis/physiology
  • von Willebrand Factor/genetics

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