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: 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
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 213 Issue 7 Pg. 1148-56 (Apr 01 2016) ISSN: 1537-6613 [Electronic] United States
• PMID: 26743845 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected].

Chemical References

• Ligands
• von Willebrand Factor

Topics

• 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, metabolism)