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Project

Staphylokinase and staphylocoagulase in infective endocarditis: experimental study in mouse models.

Blood coagulation, infection and inflammation are closely related processes. This project investigates the activation of coagulation and of blood platelets, respectively fibrinolysis during invasive Staphylococcus aureus (S. aureus) infections, in particular during infectious endocarditis (IE). In endocarditis, vegetations develop on the heart valves, primarily consisting of fibrin, blood platelets and bacteria. Fibrin formation by the host constitutes a first defense mechanism to limit infections. However, S. aureus secretes the plasminogen activator staphylokinase, which plays a role in the diffusion of bacteriea in teh host, as a consequence of fibrinolytic activation and proteolysis of extracellular matrix. The importance of staphylokinase a a virulence factor is not understood and will be addressed in vitro and in vivo in a transgenic mouse model with overexpression of human Glu-plasminogen. S. aureus also produces staphylocoagulase, which activates prothrombin and causes fibrin formation. The importance of this process for the virulence of S. aureus will be investigated in a mouse model, after hydrodynamic gene transfer of human prothrombin. Bacterial adhesion to endothelial cells is mediated primarily via fibrinectin and fibrin(ogen) of the host. Adhesion of bacteria and blood platelets, as well as the accompanying inflammatory respons will be investigated in an in vitro model of bacterial endocarditis, in perfussion chambers. The exertise present in the Center for Molecular and Vascular Biology and the clinical units of Infectious diseases and Microbiology of the UZ. K.U.Leuven will be combined to realize this project.
Date:1 Jan 2010 →  31 Dec 2013
Keywords:Hemostasis, Infection, Endocarditis, Fibrinolysis, Platelets, Fibrin
Disciplines:Microbiology, Systems biology, Laboratory medicine, Hematology, Cardiac and vascular medicine