This project has been designed in order to contribute to the development of a novel technology consisting to use bacteriophage lytic enzymes as agents for controlling bacterial populations on human mucosal membranes. These tissues are the reservoir for man y pathogenic bacteria found in the environment (i.e., pneumococci, staphylococci, streptococci). In most instances, it is this mucosal reservoir that is the focus of infection in the population. By reducing or eliminating this reservoir of pathogens in the community and controlled environments (i.e., hospitals and nursing homes), the incidence of disease will be markedly reduced. Because of the fear of developing resistances, antibiotics are not indicated. Thus, lytic enzymes may provide a good alternative. Cpl-1, a pneumococcal phage lysozyme has been chosen as a model. S. pneumoniae is a leading cause of acute otitis media, meningitis, pneumoniae, and sepsis. It is becoming increasingly resistant to multiple classes of antimicrobial agents. Because the hal f-life of Cpl-1 in the blood of mice is relatively short and is thought to be insufficient to obtain complete eradication of pneumococci, we propose to encapsulate it into liposomes. During the outgoing period, the antimicrobial activity and the residence time on mucosal membrane of different liposomal preparations will be tested in mice. The acquired knowledge will then be applied, in the laboratory of the return host, in order to develop a phase I human clinical trial with the more effective combination.
This project will be a great asset to the scientific career of the candidate, providing him all the necessary tools to develop his own infectious disease program. Moreover, the project will significantly increase the scientific expertise and attractiveness of the European Research Area. In fact, it is the first time that a bacteriophage lytic enzyme is proposed for human clinical trials.
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