Descrizione del progetto
I batteri commensali come strumento nello sviluppo del trattamento contro i patogeni persistenti agli antibiotici
Le cellule persistenti sono cellule dormienti nelle popolazioni microbiche, altamente tolleranti agli antibiotici e associate alla diffusione della resistenza agli antimicrobici attraverso elementi genetici mobili. Diversi batteri commensali abitano le superfici delle mucose e dell’epidermide e svolgono un ruolo importante nella difesa contro gli agenti patogeni. Questi batteri inibiscono la crescita dei patogeni respiratori, producendo segnali antimicrobici, competendo per le sostanze nutritive e per lo spazio e inducendo risposte protettive del sistema immunitario. Finanziato dal programma di azioni Marie Skłodowska-Curie, il progetto PERSIST utilizzerà una combinazione di strumenti basati sull’omica e modelli murini e patogeni per individuare le cellule persistenti commensali capaci di sostituire i patogeni persistenti. L’obiettivo del progetto è lo sviluppo di opzioni di trattamento contro le infezioni persistenti e il trasferimento orizzontale di resistenza agli antimicrobici.
Obiettivo
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.
Campo scientifico
- 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
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
75724 Paris
Francia