Objective
Antibiotic resistance is a major threat to global health, associated with ≈ 5 million deaths annually. While the field has largely focused on the emergence of stable resistance through mutation or horizontal gene transfer, a critical evolutionary unstable intermediate remains underexplored: heteroresistance (HR). In HR, a rare subpopulation within a main susceptible bacterial population exhibits transient high-level resistance — a phenotype that enables survival and growth under antibiotic pressure and paves the way to stable resistance. HR is often caused by increased copy number of resistance genes with low expression or activity. While cells carrying a single gene copy are susceptible, those with elevated copy numbers become resistant, and can replicate under antibiotic exposure, potentially leading to treatment failure.
This project proposes a paradigm shift in our understanding of resistance evolution. Recent discoveries from our lab have revealed, across diverse bacterial pathogens, three novel and prevalent mechanisms by which HR emerges through increased gene copy number. These mechanisms generate subpopulations that evade antibiotic killing, yet revert rapidly in the absence of selection allowing the main population to remain fit. This duality makes HR an exceptionally flexible, but clinically dangerous, adaptive strategy. Despite its significance, the evolutionary origin(s) and consequences of HR remain unknown. This proposal seeks to fill that critical gap. We will (i) define the genetic and selective conditions that allow susceptible populations to evolve HR; (ii) determine how HR acts as a stepping stone toward stable resistance; and (iii) explore the potential of HR to promote horizontal gene transfer of resistance genes. By resolving these fundamental unknowns, this project will establish HR as a central driver in the evolution of antimicrobial resistance and inform future diagnostics and treatment 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.
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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.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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.
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-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
751 05 Uppsala
Sweden
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.