Descripción del proyecto
Bacterias comensales como herramienta para desarrollar tratamientos contra patógenos persistentes a los antibióticos
Los persistentes son células latentes en poblaciones microbianas que poseen una tolerancia extremadamente alta a los antibióticos y están relacionados con la propagación de la resistencia a los antimicrobianos a través de elementos genéticos móviles. Diversas bacterias comensales habitan en las superficies epidérmicas y de las mucosas, y desempeñan una importante función de defensa contra los patógenos. Estas bacterias inhiben el crecimiento de patógenos respiratorios generando señales antimicrobianas, compitiendo por los nutrientes y el espacio, e induciendo respuestas protectoras del sistema inmunitario. El proyecto PERSIST, financiado por las Acciones Marie Skłodowska-Curie, utilizará una combinación de herramientas basadas en la ómica con modelos murinos y de patógenos para identificar los persistentes comensales capaces de desplazar a los persistentes patógenos. El objetivo del proyecto es crear opciones terapéuticas contra infecciones persistentes y la transferencia horizontal de la resistencia a los antimicrobianos.
Objetivo
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.
Ámbito científico
- 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
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Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
75724 Paris
Francia