Project description
Antimicrobial recalcitrance in multidrug-resistant ESKAPE pathogens
Antimicrobial resistance (AMR) is a growing silent pandemic that complicates infection treatment. Recalcitrance, in which susceptible bacteria resist antibiotics and cause recurrent infections, presents a significant challenge. The ESKAPE pathogens are particularly known for their multi-drug resistance. Supported by the Marie Skłodowska-Curie Actions programme, the MAREE project will investigate Enterococcus faecium (Efm) and the Enterobacter cloacae complex (Ecc) by analysing the proteome associated with antibiotic recalcitrance. The project aims to identify the stressors and antibiotics that induce this recalcitrance, evaluate the proteome and phosphoproteome of resistant bacteria, and validate candidate proteins and pathways through mutagenesis and phenotypic studies. The findings are expected to help identify new protein targets for developing therapies against AMR.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine pneumology
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences microbiology bacteriology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2022-PF-01
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35042 Rennes
France
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