Project description
Commensal bacteria as a tool in the development of treatment against pathogenic antibiotic persisters
Persisters are dormant cells in microbial populations that are highly tolerant to antibiotics and associated with the spread of antimicrobial resistance (AMR) via mobile genetic elements. Diverse commensal bacteria inhabit mucosal and epidermal surfaces, playing an important role in defence against pathogens. These bacteria inhibit the growth of respiratory pathogens, producing antimicrobial signals, competing for nutrients and space, and inducing immune system protective responses. Funded by the Marie Skłodowska-Curie Actions programme, the PERSIST project will use a combination of omics-based tools with murine and pathogen models to identify the commensal persisters capable of displacing pathogenic persisters. The project’s objective is the development of treatment options against persistent infections and the horizontal transfer of AMR.
Objective
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.
Fields of science
- 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
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
75724 Paris
France