Project description
A Trojan horse strategy to combat gram-negative antibiotic resistance
Antimicrobial resistance has become a major global health problem, making it difficult to cure even the easily treatable infections. Supported by the Marie Skłodowska-Curie Actions programme, the SYNTH HORSE project aims to tackle the problem of antimicrobial resistance with regard to Gram-negative bacteria such as Acinetobacter baumannii and Pseudomonas aeruginosa that are resistant due to their impermeable outer membrane. This project will create siderophore-teixobactin conjugates that can use the iron transport machinery of the bacterium for delivery of the antibiotic into cells. More precisely, the SYNTH HORSE project will synthesise about 60 conjugates, analyse their anti-microbial activity, resistance capacity and cell uptake as well as determine the most effective candidates against multidrug resistance.
Objective
Antimicrobial resistance (AMR) could cause 10 million deaths annually by 2050, with multidrug-resistant Gram-negative pathogens such as Acinetobacter baumannii and Pseudomonas aeruginosa listed by WHO as critical priorities. Current antibiotics fail against these species because their outer membrane blocks entry. Teixobactin, discovered in 2015, kills Gram-positive bacteria without resistance by binding the highly conserved lipid II motif, but it cannot reach this target in Gram-negatives.
SYNTH-HORSE introduces a first-in-class strategy: siderophore–teixobactin conjugates (STCs). By hijacking bacterial iron-uptake pathways—the clinically validated “Trojan Horse” mechanism—STCs deliver resistance-avoidant teixobactins into Gram-negative cells. The project will: (i) synthesise ~60 STCs across diverse teixobactin analogues, siderophores (catecholate, MECAM, DOTAM) and linkers; (ii) test antibacterial potency, bactericidal activity and resistance frequency; and (iii) validate uptake and lipid II engagement. By month 24, ≥10 optimised STCs will be delivered to tackle MDR Gram negative bacteria.
The fellowship combines cutting-edge chemistry, microbiology, and industrial translation. Hosted at the University of Liverpool (leaders in synthetic teixobactins), with a 5-month secondment at HZI Germany (antibiotic uptake biology) and training at Bachem UK (green peptide synthesis, scale-up), the Fellow will gain unique interdisciplinary, intersectoral, and international (3i) expertise. Outcomes include IP-ready leads, FAIR/Green Charter-aligned workflows, high-impact publications, and wide dissemination from science to policy.
Impact: SYNTH-HORSE delivers a breakthrough Gram-negative antibiotic platform, transforms the researcher into a future AMR leader, and contributes to EU missions on health, innovation, and sustainability.
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
- natural sciences biological sciences biochemistry biomolecules
- 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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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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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.
L69 7ZX LIVERPOOL
United Kingdom
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