Project description
How prophages affect carbapenem-resistant pOXA-48 plasmid in enterobacteria
Antimicrobial resistance (AMR), especially carbapenem-resistant Enterobacterales, represents a global health crisis. Prophages may play a key role in the spread of AMR plasmids among bacteria. Supported by the Marie Skłodowska-Curie Actions programme, the PlasPhage project will investigate how prophages affect the stability of the carbapenem-resistant pOXA-48 plasmid in Enterobacterales. It will map the interactions between prophages and pOXA-48, assess their impact on plasmid fitness and stability, and explore the molecular mechanisms involved. The project will create a functional map of the prophage-plasmid interactome in high-risk pathogens and develop a framework for predicting plasmid-mediated AMR. Collaborating with patient-derived isolates will ensure the research’s clinical relevance. Findings could lead to new phage-based therapies.
Objective
Antimicrobial resistance (AMR) is a global health crisis, with carbapenem-resistant Enterobacterales among the most urgent threats. The epidemiological success of AMR plasmids depends on their interactions with bacterial hosts, yet the factors shaping these associations remain poorly understood. I hypothesize that prophages, ubiquitous integrated viruses of bacteria, are a critical, overlooked force shaping the distribution of AMR plasmids. PlasPhage will determine if prophages act as compatibility factors of critical carbapenem-resistance plasmids by shaping their fitness cost and stability. Focusing on the clinically-relevant pOXA-48 plasmid, this project aims to: 1) map the landscape of prophage-pOXA-48 interactions in clinical Enterobacterales; 2) quantify their impact on plasmid fitness and persistence; 3) elucidate the underlying molecular mechanisms. To address this, I will combine state-of-the-art high-throughput genomics, functional screenings, evolutionary assays, mathematical modelling, and molecular genetics. This will significantly progress the field by: 1) Obtaining the first functional map of the prophage-plasmid interactome in high-risk pathogens; 2) A new predictive framework for plasmid-mediated AMR evolution integrating prophages; 3) Elucidation of key molecular mechanisms of plasmid-prophage cross-talk. By using patient-derived isolates and a non-academic placement in a clinical microbiology setting, PlasPhage ensures translational relevance. Identifying prophage factors that destabilise pOXA-48 plasmids could inspire phage-based therapies that exploit natural conflicts to eliminate AMR plasmids from pathogens. By combining my expertise in phage biology with the host lab’s strength in plasmid biology and the placement’s clinical AMR expertise, this interdisciplinary fellowship will uniquely position me to lead research on the fundamental biology of mobile genetic elements, informing the next generation of anti-AMR strategies.
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 genetics
- natural sciences biological sciences microbiology virology
- medical and health sciences clinical medicine clinical microbiology
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance antibiotic resistance
- natural sciences mathematics applied mathematics mathematical model
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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-2025-PF
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28006 Madrid
Spain
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