Objective
Antibiotic resistance is increasing globally at such a pace that many experts fear the dawn of the post-antibiotic era if we fail to meet the urgent need for novel therapeutics. We evaluated if the working hypothesis of the MANGO ERC project that protein aggregation is driven by sequence specific interactions can be exploited to generate aggregates that are specifically toxic to bacteria without affecting mammalian cells. In particular we examined if peptides encoding aggregation-prone sequence segments of bacterial proteins can display antimicrobial activity by initiating aggregation in bacteria but not in mammalian cells. Unbiased in vitro screening of aggregating peptides lead to the identification of several hits that are strongly bactericidal against drug resistant gram+ S aureus strains, and others against pathogenic gram- E coli strains. The peptides cured mice from bacterial sepsis without apparent toxic side effects. The peptides enter and accumulate in the bacterial cytosol where they cause aggregation of bacterial polypeptides and the formation of inclusion bodies. Although the precise chain of events that leads to cell death remains to be elucidated, the ability to tap into aggregation-prone sequences of bacterial proteomes to elicit antimicrobial activity represents a rich and unexplored chemical space to be mined in search of novel therapeutic strategies to fight infectious diseases that are increasingly threatening global healthcare. However, given the novelty of this concept, the viability of aggregating peptides as antimicrobial therapeutics needs to be further advanced in order to consolidate the already significant interest from the pharmaceutical industry. In the current proposal we outline a series of experiments designed to address some of the key questions that were raised by potential investors and experts from the pharmaceutical sector to whom we presented the current data package.
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 health sciences infectious diseases
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance antibiotic resistance
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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-POC - Proof of Concept 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-2017-PoC
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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.
9052 ZWIJNAARDE - GENT
Belgium
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.