Project description
Antimicrobial resistance: evolution and handling
Antibiotics misuse has led to the development of antimicrobial resistance (AMR) in bacteria. AMR genes are transferred in bacteria horizontally via mobile genetic elements such as plasmids and allow bacteria to survive antibiotics. However, recent research has found that AMR plasmids also induce changes in the bacterial host cell’s physiology and antibiotic susceptibility. Funded by the European Research Council, the PLAS-FIGHTER project aims to develop new strategies against plasmid-mediated AMR by identifying specific targets in plasmid-carrying cells and testing inhibitors of these targets in a wide range of bacterial strains in varying ecological conditions. This multidisciplinary approach will contribute to the development of novel strategies against AMR.
Objective
The discovery of antibiotics revolutionised the fight against infectious diseases and paved the way for modern medicine. However, widespread use of antibiotics has driven rampant evolution of antimicrobial resistance (AMR) in bacteria. The main route for AMR acquisition in clinically important bacteria is the horizontal transfer of plasmids (conjugation-competent mobile genetic elements) carrying resistance genes. AMR plasmids allow bacteria to survive antibiotics, but they also entail physiological alterations in the host cell. Recent results from my group and others reveal that AMR plasmids (i) produce a shared set of physiological alterations in the bacterial host and (ii) induce changes in host antibiotic susceptibility profiles. The goal of PLAS-FIGHTER is to exploit plasmid-induced physiological effects in bacteria to develop new ecology- and evolution-informed strategies against plasmid-mediated AMR. First, we will use genome-wide CRISPRi screening technology to dissect the molecular basis and functional consequences of plasmid-induced physiological effects in clinical bacteria at an unprecedented level of resolution, revealing new specific targets in AMR plasmid-carrying cells. Second, we will perform high-throughput susceptibility assays, using inhibitors of the targets revealed in the first objective and a wide range of antibiotics in a collection of paired isogenic plasmid-carrying & plasmid-free bacterial strains of the highest clinical relevance. Crucially, we will perform experiments and test candidate treatments in a gradient of increasing ecological complexity, in terms both of community composition (from monocultures to human gut communities) and habitat structure (from in vitro lab cultures to the mouse gut). In PLAS-FIGHTER, I will build on my established expertise and pioneering results to develop a novel, multidisciplinary, ground-breaking project that will open up new research avenues towards ecology- and evolution-informed 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 microbiology bacteriology
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
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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)
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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
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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-ERC - HORIZON ERC Grants
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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) ERC-2022-COG
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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.
28006 MADRID
Spain
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