Staphylococcus aureus endocarditis: distinct mechanisms of bacterial adhesion to damaged and inflamed heart valves

Laurens Liesenborghs, Severien Meyers, Marleen Lox, Maarten Criel, Jorien Claes, Marijke Peetermans, Sander Trenson, Greetje Vande Velde, Pieter Vanden Berghe, Pieter Baatsen, Dominique Missiakas, Olaf Schneewind, Willy E Peetermans, Marc F Hoylaerts, Thomas Vanassche, Peter Verhamme

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Aims: The pathogenesis of endocarditis is not well understood resulting in unsuccessful attempts at prevention. Clinical observations suggest that Staphylococcus aureus infects either damaged or inflamed heart valves. Using a newly developed endocarditis mouse model, we therefore studied the initial adhesion of S. aureus in both risk states.

Methods and results: Using 3D confocal microscopy, we examined the adhesion of fluorescent S. aureus to murine aortic valves. To mimic different risk states we either damaged the valves with a surgically placed catheter or simulated valve inflammation by local endothelium activation. We used von Willebrand factor (VWF) gene-deficient mice, induced platelet and fibrinogen depletion and used several S. aureus mutant strains to investigate the contribution of both host and bacterial factors in early bacterial adhesion. Both cardiac valve damage and inflammation predisposed to endocarditis, but by distinct mechanisms. Following valve damage, S. aureus adhered directly to VWF and fibrin, deposited on the damaged valve. This was mediated by Sortase A-dependent adhesins such as VWF-binding protein and Clumping factor A. Platelets did not contribute. In contrast, upon cardiac valve inflammation, widespread endothelial activation led to endothelial cell-bound VWF release. This recruited large amounts of platelets, capturing S. aureus to the valve surface. Here, neither fibrinogen, nor Sortase A were essential.

Conclusion: Cardiac valve damage and inflammation predispose to S. aureus endocarditis via distinct mechanisms. These findings may have important implications for the development of new preventive strategies, as some interventions might be effective in one risk state, but not in the other.

Original languageEnglish
JournalEuropean Heart Journal
Issue number39
Pages (from-to)3248-3259
Number of pages12
Publication statusPublished - 2019


  • Animals
  • Aortic Valve/injuries
  • Bacterial Adhesion
  • Blood Platelets
  • Coagulase/metabolism
  • Disease Models, Animal
  • Endocarditis, Bacterial/metabolism
  • Endothelium/metabolism
  • Female
  • Fibrin/metabolism
  • Inflammation/complications
  • Male
  • Mice
  • Platelet Membrane Glycoproteins/metabolism
  • Staphylococcal Infections/complications
  • Staphylococcus aureus/metabolism
  • von Willebrand Factor/genetics


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