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Thromb Haemost 2009; 101(03): 495-504
DOI: 10.1160/TH08-06-0395
Wound Healing and Inflammation/Infection
Schattauer GmbH

Contribution of (sub)domains of Staphylococcus aureus fibronectin-binding protein to the proinflammatory and procoagulant response of human vascular endothelial cells

Ruth Heying
1   Department of Paediatric Cardiology, University Children‘s Hospital, Duesseldorf, Germany
2   Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
,
Joke van de Gevel
2   Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
,
Yok-Ai Que
3   Department of Critical Care Medicine, CHUV and University of Lausanne, Lausanne, Switzerland
,
Lionel Piroth
4   Infectious Diseases Department, University Hospital, Dijon, France
,
Philippe Moreillon
5   Institutes of Fundamental Microbiology, UNIL, Lausanne, Switzerland
,
Henry Beekhuizen
2   Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received: 20 June 2008

Accepted after major revision: 19 February 2008

Publication Date:
24 November 2017 (online)

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Summary

The Staphylococcus aureus fibronectin (Fn) -binding protein A (FnBPA) is involved in bacterium-endothelium interactions which is one of the crucial events leading to infective endocarditis (IE). We previously showed that the sole expression of S. aureus FnBPA was sufficient to confer to non-invasive Lactococcus lactis bacteria the capacity to invade human endothelial cells (ECs) and to launch the typical endothelial proinflammatory and procoagulant responses that characterize IE. In the present study we further questioned whether these bacterium-EC interactions could be reproduced by single or combined FnBPA subdomains (A, B, C or D) using a large library of truncated FnBPA constructs expressed in L. lactis. Significant invasion of cultured ECs was found for L. lactis expressing the FnBPA subdomains CD (aa 604–877) or A4+16 (aa 432–559). Moreover, this correlates with the capacity of these fragments to elicit in vitro a marked increase in EC surface expression of both ICAM-1 and VCAM-1 and secretion of the CXCL8 chemokine and finally to induce a tissue factor-dependent endothelial coagulation response. We thus conclude that (sub)domains of the staphylococcal FnBPA molecule that express Fn-binding modules, alone or in combination, are sufficient to evoke an endothelial proinflammatory as well as a procoagulant response and thus account for IE severity.

Keywords

Bacterial infection - endothelial cells - inflammation - thrombosis - tissue factor / factor VII
 

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