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Mechanisms of Antibiotic Recalcitrance in ESKAPE pathogens
Antimicrobial resistance (AMR) is the silent pandemic uprising for the past decades that challenges practitioners to everyday life. In this context, more and more infections have become harder to treat, even in absence of genetic... Antimicrobial resistance (AMR) is the silent pandemic uprising for the past decades that challenges practitioners to everyday life. In this context, more and more infections have become harder to treat, even in absence of genetic markers for AMR. This phenomenon, called recalcitrance, is related to the ability of susceptible bacteria to overcome antibiotic treatment and to reinitiate infection contributing to antibiotic failures and resistance emergence. Previous studies have described the involvement of a phenotypic switch leading to recalcitrance but underlying mechanism remain poorly understood. ESKAPE (standing for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) pathogens are the most prevalent causative agents in common recurrent healthcare-associated infections as well as well-known for their multidrug resistant phenotype and are the best candidates to understand recalcitrance. Hereby, we propose to investigate two of them, E. faecium (Efm) and E. cloacae complex (Ecc) by studying the proteome involved in recalcitrance. To identify any protein and/or pathway of interest, we will (i) identify which stress and bactericidal antibiotic induce recalcitrance both in Efm and Ecc; (ii) evaluate proteome and phosphoproteome of isolated antibiotic-recalcitrant bacteria; and (iii) confirm functionality of candidate proteins/pathways by mutagenesis and phenotypic approaches (in vitro and in cellulo) with the expertise of Prof. Helaine at Harvard Medical School (HMS) in Boston (secondment). Finding potential protein targets can highlight new candidates to further develop new therapies to overcome the rising of AMR. ver más
30/06/2025
196K€
Duración del proyecto: 25 meses Fecha Inicio: 2023-05-16
Fecha Fin: 2025-06-30

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-05-16
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
Presupuesto El presupuesto total del proyecto asciende a 196K€
Líder del proyecto
UNIVERSITE DE RENNES No se ha especificado una descripción o un objeto social para esta compañía.