Projektbeschreibung
Innovativer Ansatz zur Überwindung der antimikrobiellen Resistenz bei gramnegativen Bakterien
Die antimikrobielle Resistenz, die mit multiresistenten Krankheitserregern einhergeht, stellt einen internationalen Gesundheitsnotstand dar. Gramnegative Bakterien verhindern eine wirksame Behandlung, indem sie ihre äußere Membran für standardtherapeutische Antibiotika undurchlässig werden lassen. Das im Rahmen der Marie-Skłodowska-Curie-Maßnahmen finanzierte Forschungs- und Ausbildungsnetz BREAKthrough zielt darauf ab, die Bakterien für Standardtherapie-Antibiotika zu sensibilisieren, indem die Durchlässigkeit ihrer Außenmembran aktiviert wird. Ziel ist es, Hemmstoffe für drei Proteinmaschinerien zu entwickeln, die für die Aufrechterhaltung der äußeren Membran verantwortlich sind. Zu den weiteren Zielen gehören die Entwicklung neuer chemischer Raumregeln für Wirkstoffe, die die äußere Membran passieren, die Entdeckung von Erhaltungsinhibitoren der Außenmembran zur Überwindung der Resistenz gegen Standardtherapie-Antibiotika und die Ausbildung von 11 Promovierenden in der Richtung der industriellen Arzneimittelentwicklung.
Ziel
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.
Wissenschaftliches Gebiet
- 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
Schlüsselbegriffe
Programm/Programme
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenFinanzierungsplan
HORIZON-TMA-MSCA-DN - HORIZON TMA MSCA Doctoral NetworksKoordinator
1348 Louvain La Neuve
Belgien