Description du projet
Une approche innovante pour vaincre la résistance aux antimicrobiens des bactéries à Gram négatif
La résistance aux antimicrobiens, associée aux agents pathogènes multirésistants, constitue une urgence sanitaire mondiale. Les bactéries à Gram négatif empêchent un traitement efficace en rendant leur membrane externe (ME) imperméable aux antibiotiques standards. Financé par le programme Actions Marie Skłodowska-Curie, le réseau de recherche et de formation BREAKthrough a pour objectif de sensibiliser les bactéries aux antibiotiques standards en rendant leur ME perméable. Le but est de développer des inhibiteurs de trois machineries protéiques responsables du maintien de la ME. Les objectifs sont notamment le développement de nouvelles règles d’espace chimique pour les médicaments traversant la ME, la découverte d’inhibiteurs de la maintenance de la ME pour surmonter la résistance aux antibiotiques standards, et la formation de 11 candidats au doctorat appelés à devenir des développeurs professionnels de médicaments industriels.
Objectif
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.
Champ scientifique
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- natural sciencesbiological sciencesmicrobiologybacteriology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
- natural sciencesbiological sciencesmolecular biology
Mots‑clés
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
HORIZON-TMA-MSCA-DN - HORIZON TMA MSCA Doctoral NetworksCoordinateur
1348 Louvain La Neuve
Belgique