Project description
Metabolic mechanisms of antimicrobial resistance
Antimicrobial resistance (AMR) is a growing global health problem, projected to cause millions of deaths and enormous economic losses by 2050. While much is known about genetic resistance, less is understood about pre-resistant bacterial cells that survive lethal antibiotic doses and pave the way for resistance. With the support of the Marie Skłodowska-Curie Actions programme, the MetEvoAMR project will study how metabolic adaptations help subpopulations of Pseudomonas aeruginosa and Acinetobacter baumannii transiently survive treatment. The research team will identify key metabolic and signalling pathways that support survival under antimicrobial stress. Findings are slated to reveal new targets that can be used to combat AMR and help design strategies to prevent the emergence of resistant bacteria.
Objective
Antimicrobial resistance (AMR) is a rising global health threat and rapid evolution of resistance against existing or newly developed antibacterial compounds is predicted to lead to 10 million deaths and $60 trillion of lost economic output by 2050. While resistance-conferring mutations, their inheritance and spread by horizontal gene transfer are increasingly well-studied, our understanding of “pre-resistant” cells’ survival and resilience in the presence of lethal antibacterial doses remains unclear. This proposal is stimulated by recent findings suggesting that the extracellular metabolic environment and metabolic adaptations play an overlooked role in transiently buffering antibiotic lethality and, therefore, increase the emergence of subpopulations of cells and their effective size that supports the evolution of antimicrobial resistance. In this proposal, I will systematically dissect mechanisms at work in subpopulations of “pre-resistant” cells of priority pathogens Pseudomonas aeruginosa and Acinetobacter baumannii that can transiently cope with antimicrobial treatment. I propose to combine my expertise in bacterial physiology with the Ralser Lab’s ultra-fast, massive-scale proteomics and phenomics technologies. I will systematically investigate the metabolic stress response in clinically relevant conditions, and identify the key metabolic and signalling processes that support the survival of subsets of challenged cells upon exposure to major classes of clinically applied antimicrobials. Finally, adaptive evolution experiments combined with CRISPR/Cas9 gene editing will validate causal effectors of identified tolerance mechanisms that precede the appearance of resistance-conveying adaptations. Here, I will acquire technical skills in innovative technologies and the host lab will benefit from my experience in working with pathogenic bacteria. I will lead public engagement efforts and disseminate scientific research outputs on an important global health issue.
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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine physiology
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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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Topic(s)
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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.
Funding Scheme
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.
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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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2021-PF-01
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10117 Berlin
Germany
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