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Thromb Haemost 2007; 97(04): 617-626
DOI: 10.1160/TH06-11-0640
Wound Healing and Inflammation/Infection
Schattauer GmbH

Fibronectin-binding proteins and clumping factor A in Staphylococcus aureus experimental endocarditis: FnBPA is sufficient to activate human 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   Division of Critical Care Medicine, Internal Medicine Department, CHUV, Lausanne, Switzerland
,
Philippe Moreillon
4   Institute of Fundamental Microbiology, UNIL, Lausanne, Switzerland
,
Henry Beekhuizen
2   Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
› Author AffiliationsFinancial support: This work was in part supported by a grant from the German Society of Cardiology, Duesseldorf, Germany.
Further Information

Publication History

Received 10 November 2006

Accepted after resubmission 15 February 2007

Publication Date:
24 November 2017 (online)

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Summary

Surface molecules of Staphylococcus aureus are involved in the colonization of vascular endothelium which is a crucial primary event in the pathogenesis of infective endocarditis (IE).The ability of these molecules to also launch endothelial procoagulant and proinflammatory responses, which characterize IE, is not known. In the present study we investigated the individual capacities of three prominent S. aureus surface molecules; fibronectinbinding protein A (FnBPA) and B (FnBPB) and clumping factor A (ClfA), to promote bacterial adherence to cultured human endothelial cells (ECs) and to activate phenotypic and functional changes in these ECs. Non-invasive surrogate bacterium Lactococcus lactis, which, by gene transfer, expressed staphylococcal FnBPA, FnBPB or ClfA molecules were used. Infection of ECs increased 50- to 100-fold with FnBPA- or FnBPB-positive recombinant lactococci. This coincided with EC activation, interleukin- 8 secretion and surface expression of ICAM-1 andVCAM-1 and concomitant monocyte adhesion. Infection with ClfA-positive lactococci did not activate EC. FnBPA-positive L. lactis also induced a prominent tissue factor-dependent endothelial coagulation response that was intensified by cell-bound monocytes. Thus S. aureus FnBPs, but not ClfA, confer invasiveness and pathogenicity to non-pathogenic L. lactis organisms indicating that bacterium-EC interactions mediated by these adhesins are sufficient to evoke inflammation as well as procoagulant activity at infected endovascular sites.

Keywords

Staphylococcus aureus - endocarditis - coagulation - fibronectin binding protein A - endothelium - activation
 

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