Project description
Employing genetics to identify the Achilles heel of bacteria
Antibiotic resistance has become a major health threat, impeding the clinical outcome of surgeries and otherwise treatable diseases. Therefore, there is a pressing need to understand the drivers of antibiotic resistance and find ways to counteract them. The EU-funded uCARE project will work under the hypothesis that bacteria use similar resistance mechanisms against antibiotics and drugs that target human molecules. To elucidate the common resistance mechanisms and networks, researchers will use chemical genetics and experimental evolution. By uncovering resistance development of human-targeted drugs, the project will help revisit current medication policies.
Objective
The evolution and spread of antibiotic resistance has become a public health concern of the utmost severity, making once treatable diseases deadly again and undermining our living standards. New therapies are imperative, but equally important are the understanding of the full repertoire of drivers of antibiotic resistance and the identification of ways to counteract them. We have recently established that ~250 non-antibiotic drugs have direct, strong and often broad antibacterial effects on human gut microbes. Moreover, preliminary data indicate that bacteria use similar general resistance mechanisms against both drugs with human targets and antibiotics. This implies that polypharmacy may be a hitherto unnoticed driver of antibiotic resistance. We will use chemical genetics and experimental evolution to systematically map the cross-resistance between human-targeted drugs and antibiotics, and elucidate underlying resistance mechanisms. Using these data, we will next seek to identify antidotes for the antimicrobial side-effects of non-antibiotic drugs, and exploit human-targeted drugs for reverting existing antibiotic resistance. At the genetic level, we will use high-throughput reverse genetics to expose the Achilles heels of bacterial cellular networks for resistance development. Finally, we will uncover the antimicrobial mode of action of tens of human-targeted drugs using thermal proteome profiling and chemical genetics. Together with the genetic information, this line of research will yield design principles and possibly new drug candidates for longer-lived, resistance-proof drug combinations. Overall, this project aims at improving our fundamental biological understanding of antibiotic resistance and the paths to prevent, delay or revert it. It can also set the basis for revisiting current medication policies. The derived principles are likely to be relevant to other diseases and therapies, in which resistance development is an 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
- natural sciences biological sciences microbiology bacteriology
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance antibiotic resistance
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - 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.
ERC-COG - Consolidator Grant
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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-2018-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.
69117 Heidelberg
Germany
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.