title: Use of a human-like low-grade bacteremia model of experimental endocarditis to study the role of Staphylococcus aureus adhesins and platelet aggregation in early endocarditis.
abstract: Animal models of infective endocarditis (IE) induced by high-grade bacteremia revealed the pathogenic roles of Staphylococcus aureus surface adhesins and platelet aggregation in the infection process. In humans, however, S. aureus IE possibly occurs through repeated bouts of low-grade bacteremia from a colonized site or intravenous device. Here we used a rat model of IE induced by continuous low-grade bacteremia to explore further the contributions of S. aureus virulence factors to the initiation of IE. Rats with aortic vegetations were inoculated by continuous intravenous infusion (0.0017 ml/min over 10 h) with 10(6) CFU of Lactococcus lactis pIL253 or a recombinant L. lactis strain expressing an individual S. aureus surface protein (ClfA, FnbpA, BCD, or SdrE) conferring a particular adhesive or platelet aggregation property. Vegetation infection was assessed 24 h later. Plasma was collected at 0, 2, and 6 h postinoculation to quantify the expression of tumor necrosis factor (TNF), interleukin 1α (IL-1α), IL-1β, IL-6, and IL-10. The percentage of vegetation infection relative to that with strain pIL253 (11%) increased when binding to fibrinogen was conferred on L. lactis (ClfA strain) (52%; P = 0.007) and increased further with adhesion to fibronectin (FnbpA strain) (75%; P < 0.001). Expression of fibronectin binding alone was not sufficient to induce IE (BCD strain) (10% of infection). Platelet aggregation increased the risk of vegetation infection (SdrE strain) (30%). Conferring adhesion to fibrinogen and fibronectin favored IL-1β and IL-6 production. Our results, with a model of IE induced by low-grade bacteremia, resembling human disease, extend the essential role of fibrinogen binding in the initiation of S. aureus IE. Triggering of platelet aggregation or an inflammatory response may contribute to or promote the development of IE.
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Tiago Rafael
authors.initials: TR
authors.lastname: Veloso
authors.forename: Aziz
authors.initials: A
authors.lastname: Chaouch
authors.forename: Thierry
authors.initials: T
authors.lastname: Roger
authors.forename: Marlyse
authors.initials: M
authors.lastname: Giddey
authors.forename: Jacques
authors.initials: J
authors.lastname: Vouillamoz
authors.forename: Paul
authors.initials: P
authors.lastname: Majcherczyk
authors.forename: Yok-Ai
authors.initials: YA
authors.lastname: Que
authors.forename: Valentin
authors.initials: V
authors.lastname: Rousson
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreillon
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Entenza
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016470:Bacteremia / Q000276:immunology*; D001422:Bacterial Adhesion / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004697:Endocarditis, Bacterial / Q000276:immunology*; D005340:Fibrinogen; D005353:Fibronectins; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D055767:Immobilized Proteins; D010974:Platelet Aggregation / Q000276:immunology*; D051381:Rats; D013211:Staphylococcus aureus / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D016207:Cytokines; D005353:Fibronectins; D055767:Immobilized Proteins; D005340:Fibrinogen