Our group uses different animal models as the in vivo read-out system of their different research activities:
The rat model of experimental endocarditis. In brief, the model is the following: an original lesion of the aortic valve is produced in rats by inserting a thin catheter trough the aortic valve leaflets, via the right carotid artery. The valvular lesion becomes rapidly recovered by sterile platelet-fibrin vegetations, which mimic cardiac vegetations in human heart disease. The damaged valves are further infected by intravenous inoculation of the rats with the test organisms and the animals develop a typical clinical and pathological picture of endocarditis within days. In the vegetation, the bacterial become embedded in a meshwork of platelet and fibrin which is practically devoid of cellular host defense mechanisms.
The animal model of experimental endocarditis has largely contributed to better understand the mechanism of bacterial pathogenesis. As an example, early experiments in experimental endocarditis clearly demonstrated the importance of valvular attachment and colonization in the development of the infection. Indeed, bacteria which cause endocarditis had the distinct capacity to adhere to damaged cardiac valves. This trait allowed the model to be regularly used for the study of the implication of bacterial adhesins in pathogenicity and the molecular mechanisms of bacterial infection.
This model is also particularly well suited to investigate the in vivo efficacy new antibacterial drugs. First, the model is therapeutically relevant because it mimics infectious endocarditis in humans. Second, the model is particularly stringent for antibiotic efficacy, because successful treatment of endocarditis essentially relies on the sole ability of the antibacterial drug to kill the bacteria inside the infected vegetations. Third, it allowed evaluating the therapeutic effect both in a PMN-free infection system, i.e., inside the cardiac vegetation, and a PMN-rich system in the infected spleens. Finally, we use a programmable infusion pump system to deliver the antibiotics, which allows to exactly simulate in animals the pharmacokinetics produced by standard administration of the compounds in humans. All in all, these advantages make the model of experimental endocarditis in rats a good predictor of the response to therapy in humans.
The mouse model of experimental septicaemia. This model is used to determine the minimum lethal dose of an organism or/and the role of a specific gene mutation in survival. Groups of mice are infected intravenously by the tail vein with varying numbers of the tests organisms. The animals are observed daily over 7 to 15 days post infection and body weight and percent survival are recorded. Colony counts in defined tissues can also be performed.