Description du sujet de thèse

Patients with cystic fibrosis are prone to severe respiratory infections caused by Mycobacterium abscessus, which, during prolonged treatment, becomes resistant to the action of certain antibiotics. Three major classes of antibiotics work against this bacterium but they do not prevent, under certain circumstances, the persistence of infection and relapses. We have discovered a new family of molecules, which are non-toxic to animals and active against M. abscessus. These compounds target, among many other, the protein responsible for clarithromycin-induced resistance, which is the central pillar of multidrug therapy to control M. abscessus infections. Using wild-type (WT) and clarithromycin-resistant planktonic strains, we demonstrated that these molecules were active against WT strains, reduced the induction of clarithromycin resistance, and retained their effect against strains that were spontaneously resistant to macrolides. Furthermore, our compounds exhibit a synergistic effect with clarithromycin, suggesting a potential new therapeutic strategy for treating M. abscessus infections. This project aims to confirm these results using CyC/macrolide combinations i) on clarithromycin-resistant clinical strains in vitro; ii) ex vivo on infected macrophages; and iii) in vivo on infected mice during infectious challenges.
The student should have knowledges of microbiology, infectiology, and cell biology.

Contexte de travail

This work thesis will be carried out in the Laboratory of engineering and macromolecular systems within the lipolysis and bacterial pathogenesis team directed by Stéphane Canaan. The team is currently composed of 6 permanent members, 4 PhD. student, 3 Post Doc and 1 master's degree. All the skills necessary for the successful of the thesis are mastered by all members of the team. Web site https://tuberculosis-lbp.wixsite.com/tuberculosis-lbpteam

Contraintes et risques

The Ph D. student will be work in a type 2 laboratory and handle type 2 pathogenic organisms. The products considered to be the most toxic will be organic solvents traditionally used for lipid extraction (chloroform, ethanol, ether).

Informations complémentaires

This project will be funded by the association Vaincre la Mucosvicidose. As such, the student will participate to meetings and symposia organized by the association. The goal being to meet and exchange with patients about our researchs