Descrizione del progetto
Un approccio innovativo per superare la resistenza antimicrobica nei batteri Gram-negativi
La resistenza agli antimicrobici, associata a patogeni multiresistenti ai farmaci, rappresenta un’emergenza sanitaria globale. I batteri Gram-negativi impediscono un trattamento efficace rendendo la loro membrana esterna impermeabile agli antibiotici standard. Finanziata dal programma di azioni Marie Skłodowska-Curie, la rete di ricerca e formazione BREAKthrough mira a sensibilizzare i batteri agli antibiotici standard, rendendo la loro membrana esterna permeabile al fine di sviluppare inibitori di tre sistemi proteici responsabili del mantenimento di quest’ultima. Tra gli obiettivi figurano lo sviluppo di nuove regole in merito allo spazio chimico per i farmaci che attraversano la membrana esterna, la scoperta di inibitori per il mantenimento della membrana esterna finalizzati al superamento della resistenza agli antibiotici standard e la formazione di 11 dottorandi in materia di sviluppo professionale di farmaci industriali.
Obiettivo
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.
Campo scientifico
- 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
Parole chiave
Programma(i)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Meccanismo di finanziamento
HORIZON-TMA-MSCA-DN - HORIZON TMA MSCA Doctoral NetworksCoordinatore
1348 Louvain La Neuve
Belgio