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

Article Article scientifique Article Fibrinogen and fibronectin binding cooperate for valve infection and invasion in Staphylococcus aureus experimental endocarditis eng 2005 author Que Y. A. author Haefliger J. A. author Piroth Lionel author Francois Patrice 0000-0002-0540-750X 28911 author Widmer Eleonora author Entenza J. M. author Sinha Bhanu Nath Manuele 104029 author Herrmann Mathias author Francioli Patrick author Vaudaux Pierre 24012 author Moreillon Philippe 756259 1627-1635 10.1084/jem.20050125 15897276 0022-1007 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212930/pdf/20050125.pdf 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. Adhesins, Bacterial/genetics/ metabolism Animals Bacterial Adhesion/ genetics Coagulase/genetics/ metabolism Endocarditis, Bacterial/metabolism/ microbiology/pathology Endothelium, Vascular/metabolism/microbiology/pathology Female Fibrinogen/metabolism Fibronectins/metabolism Heart Valves/metabolism/ microbiology/pathology Lactococcus lactis/genetics/pathogenicity Protein Binding Protein Structure, Tertiary/genetics Rats Rats, Wistar Sequence Deletion Spleen/metabolism/microbiology/pathology Staphylococcal Infections/metabolism/ microbiology/pathology Staphylococcus aureus/genetics/ pathogenicity Dewey 616 56 Département de médecine 221 false The Journal of experimental medicine 201 10 9299b99a-436c-43e0-a5f2-2f6915a65ee4 Article Restricted file1.pdf 1450560 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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Fibrinogen and fibronectin binding cooperate for valve infection and invasion in Staphylococcus aureus experimental endocarditis	The Journal of experimental medicine			2005	563	0

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Sinha, Bhanu Nath Manuele