Utilisation des bactériophages comme thérapie lors d'une infection à Pseudomonas aeruginosa dans le cadre de la mucoviscidose : efficacité et innocuité

摘要

Repetitive antibiotic treatments against Pseudomonas aeruginosa in cystic fibrosis patients lead to the emergence of multi-resistant strains calling for new therapeutic strategies. One of the most promising approach seems to be the use of bacteriophages. In Eastern Europe successful human treatments with bacteriophages are ongoing since decades, while in Western Europe the interest for phage therapy is still weak. Notably, no data are available on the potential application of bacteriophages to treat pulmonary infections in CF patients. In this study, we first demonstrated in mice model that bacteriophages were able to treat a lethal pulmonary infection caused by a clinical strain of P. aeruginosa. We also studied the efficacy of different bacteriophages to reduce in vitro a P. aeruginosa biofilm.In a second time, we evaluate inflammation induced by bacteriophages which was found to be negligible in different models in vitro and in vivo. The transepithelial ion transport, a crucial function in cystic fibrosis, was also evaluated by measuring the nasal potential difference (npd) in mice. When mice were treated with bacteriophages, npd values did not differ from the reference ones, demonstrating an aspect of bacteriophages safety. Finally, in order to develop this therapeutic approach towards clinical trials, we successfully developed a protocol for the evaluation of bacteriophages ability to infect bacteria within sputum of cystic fibrosis patients. Our work focusing on both safety and efficacy of bacteriophages treatments in a CF context should contribute to the future developments of clinical trials