PERSIST | Antibiotic persisters during infection: a tail of intestinal dominion

Summary
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.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101028544
Start date: 01-11-2021
End date: 31-10-2024
Total budget - Public funding: 257 619,84 Euro - 257 619,00 Euro
Cordis data

Original description

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.

Status

TERMINATED

Call topic

MSCA-IF-2020

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2020
MSCA-IF-2020 Individual Fellowships