The Journal of Experimental Medicine
StemCell Technologies
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Published 16 May 2005. doi:10.1084/jem.20050125
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 10, 1627-1635
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ARTICLE

 Fibrinogen and fibronectin binding cooperate for valve infection and invasion in Staphylococcus aureus experimental endocarditis

Yok-Ai Que2,3, Jacques-Antoine Haefliger4, Lionel Piroth1, Patrice François5, Eleonora Widmer1, José M. Entenza1,3, Bhanu Sinha6, Mathias Herrmann7, Patrick Francioli3, Pierre Vaudaux5, and Philippe Moreillon1

1 Department of Fundamental Microbiology, University of Lausanne, 1015 Lausanne, Switzerland
2 Medical Intensive Care Unit, Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
3 Service of Infectious Diseases, Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
4 Laboratory of Molecular Biology, Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
5 Division of Infectious Diseases, University Hospital of Geneva,1211 Geneva 14, Switzerland
6 Institute of Medical Microbiology, University Hospital of Münster, 48149 Münster, Germany
7 Institute of Medical Microbiology and Hygiene, University of the Saarland, 66421 Homburg, Germany

CORRESPONDENCE Philippe Moreillon: Philippe.Moreillon{at}unil.ch

The expression of Staphylococcus aureus adhesins in Lactococcus lactis identified clumping factor A (ClfA) and fibronectin-binding protein A (FnBPA) as critical for valve colonization in rats with experimental endocarditis. This study further analyzed their role in disease evolution. Infected animals were followed for 3 d. ClfA-positive lactococci successfully colonized damaged valves, but were spontaneously eradicated over 48 h. In contrast, FnBPA-positive lactococci progressively increased bacterial titers in vegetations and spleens. At imaging, ClfA-positive lactococci were restricted to the vegetations, whereas FnBPA-positive lactococci also invaded the adjacent endothelium. This reflected the capacity of FnBPA to trigger cell internalization in vitro. Because FnBPA carries both fibrinogen- and fibronectin-binding domains, we tested the role of these functionalities by deleting the fibrinogen-binding domain of FnBPA and supplementing it with the fibrinogen-binding domain of ClfA in cis or in trans. Deletion of the fibrinogen-binding domain of FnBPA did not alter fibronectin binding and cell internalization in vitro. However, it totally abrogated valve infectivity in vivo. This ability was restored in cis by inserting the fibrinogen-binding domain of ClfA into truncated FnBPA, and in trans by coexpressing full-length ClfA and truncated FnBPA on two separate plasmids. Thus, fibrinogen and fibronectin binding could cooperate for S. aureus valve colonization and endothelial invasion in vivo.

Abbreviations used: ClfA, clumping factor A; EM, electron microscopy; FnBP, fibronectin-binding protein; HUVEC, human umbilical vein endothelial cell; ID80, 80% infective dose; PAS, periodic acid schiff.


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