Projet BREAKthrough (Horizon Europe, appel à projets 2021)
Action : Doctoral Networks
Panel : Life Sciences
Statut du projet : SIGNED

Antimicrobial resistance, which is caused by multi-drug-resistant bacterial pathogens is a global health emergency. Gram-negative bacteria (GNB) notably hinder effective treatment because of their impermeable outer membrane (OM). Consequently, many standard-of-care (SOC) antibiotics cannot access intracellular targets in GNB. The objective of the BREAKthrough European Training Network (ETN) is to sensitise GNB to these antibiotics by making their OM permeable. To this end, we will develop inhibitors of three protein machineries that are responsible for OM maintenance. Importantly, many known antibacterial agents have characteristics different from drugs that are directed against targets in mammalian cells. To define better rules for antibacterial drug development a data hub will be created to assemble information on the physico-chemical characteristics of molecules that can pass the OM. To achieve these goals, a multi-disciplinary academic-industrial consortium has been assembled with organic chemists, computational chemists and specialists in high-throughput drug screening, zebrafish infection models, bacterial morphogenesis and the molecular biology of the three targets. The expected outcomes of the BREAKthrough ETN include (i) the development of new chemical space rules for drugs that need to cross the OM, (ii) the discovery of new inhibitors that interfere with OM maintenance to overcome the insensitivity of Gram-negative pathogenic bacteria towards SOC antibiotics and (iii) providing 10 Early Stage Researchers with scientific, technical, business and transferable skills to become professional drug developers with a keen eye for the hurdles in the development of these drugs in an industrial context.

Mots clés : bacterial outer membrane, gram negative bacteria, bam, lpt, lipopolysaccharide, ld transpeptidases, zebrafish infection model, peptidoglycan, antimicrobial, potentiator

Participants :
- Naicons srl (Italie) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 259437.6 €
- Amsterdam University Medical Centers (Pays-Bas) — Partner, beneficiary, Recherche, subvention : 274370.4 €
- Université de Ljubljana (Slovénie) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 242179.2 €
- Accelopment (Switzerland) (Suisse) — Partner, associated partner, Organismes privés (hors enseignement), subvention : 0.0 €
- Université libre d'Amsterdam (Pays-Bas) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 274370.4 €
- syncom (Pays-Bas) — Partner, associated partner, Organismes privés (hors enseignement), subvention : 0.0 €
- CERCA Institution (Espagne) — Partner, beneficiary, Recherche, subvention : 237972.8 €
- Centre national de la recherche scientifique (France) — Partner, beneficiary, Recherche, subvention : 282693.6 €
- Université de Newcastle upon Tyne (Royaume-Uni) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Université de Milan (Italie) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 518875.2 €
- Roche (Switzerland) (Suisse) — Partner, associated partner, Organismes privés (hors enseignement), subvention : 0.0 €
- Université de Barcelone (Espagne) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Université Rovira i Virgili (Espagne) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Université du Queensland (Australie) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Institute of Chemical Research of Catalonia (Espagne) — Partner, beneficiary, Recherche, subvention : 251971.2 €
- Université catholique de Louvain (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 262620.0 €
- Syngulon (Belgique) — Partner, associated partner, Organismes privés (hors enseignement), subvention : 0.0 €