Description du projet
Des bactéries commensales pour développer des traitements contre les cellules persistantes aux antibiotiques
Les cellules persistantes sont des cellules dormantes dans les populations microbiennes qui sont hautement tolérantes aux antibiotiques et associées à la propagation de la résistance aux antimicrobiens (RAM) via des éléments génétiques mobiles. Différentes bactéries commensales vivent à la surface des muqueuses et de l’épiderme et jouent un rôle important dans la défense contre les agents pathogènes. Ces bactéries inhibent la croissance des agents pathogènes respiratoires, en produisant des signaux antimicrobiens, en se disputant les nutriments et l’espace, et en induisant des réponses protectrices du système immunitaire. Financé par le programme Actions Marie Skłodowska-Curie, le projet PERSIST utilisera une combinaison d’outils omiques et de modèles murins et pathogènes pour identifier les cellules persistantes commensales capables de déplacer les cellules persistantes pathogènes. L’objectif du projet est le développement d’options de traitement contre les infections persistantes et le transfert horizontal de la RAM.
Objectif
Persisters are transiently non-growing bacteria cells that evade antibiotic treatment and immune response. Persisters have been associated with antibiotic treatment failure and the spread of antibiotic-resistance (AMR) through mobile genetic elements. Consequently, persisters contribute significantly to the morbidity and mortality of bacterial infections, and increased medical costs. Although it is known that many pathogenic bacteria are able to form persisters, the occurrence of persistence among commensal bacteria is yet unexplored. This project aims to identify and exploit commensal persisters able to antagonise and displace pathogenic persisters, offering opportunities for the development of innovative treatment options to arrest both the relapse of persistent infections and the horizontal transfer of AMR. To this effect, I will use a combination of cutting-edge omics-based tools, in vivo murine models and the well-established and relevant Salmonella enterica serovar Typhimurium enteric model pathogen. After identifying commensal species forming persisters (WP1), I will assess the ability of these persisters to compete with Salmonella persisters during infection (WP2) and to arrest in vivo horizontal gene transfer from Salmonella persisters to intestinal microbiota (WP3). My goal is to become a leading academic scientist in the intertwining fields of antibiotic-resistance and antibiotic-persistence, with emphasis on the involvement of persister cells in the maintenance and spread of mobile genetic elements encoding AMR. The state-of-the-art computational and experimental training at the pioneering groups of in vivo persister biology at Harvard Medical School (HMS) in USA and of genome spatial organization at the Institut Pasteur (IP) in France will be instrumental towards achieving my goal. Apart from empowering my career track, this fellowship will foster future collaborations between HMS and IP, and promote transfer of knowledge in Europe.
Champ scientifique
- natural sciencesbiological sciencesmicrobiologybacteriology
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Mots‑clés
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
75724 Paris
France