Description du projet
Les antibiotiques hautement sélectifs peuvent combattre les pathogènes humains hautement résistants
Les antibiotiques (qui signifient littéralement «contre la vie») tuent les bactéries. Comme nos organismes abritent de nombreuses «bonnes» bactéries, les antibiotiques doivent être sélectifs. Les ribosomes sont le site de la synthèse protéique et la cible de nouveaux traitements en cours de développement par NEXTER. L’approche essentielle consiste à cibler certaines parties de ribosomes spécifiques à certaines espèces de bactéries. Grâce à cette stratégie, les scientifiques ont stoppé la croissance d’une souche multirésistante de Staphylococcus aureus (S. aureus), un agent pathogène humain important qui cause des infections en milieu clinique et communautaire. De plus, ces produits thérapeutiques synthétiques sont dégradables, ce qui signifie qu’ils réduiront la contamination de l’environnement et le développement de souches résistantes. L’équipe cible maintenant d’autres agents pathogènes et prévoit de commercialiser bientôt cette technologie pionnière.
Objectif
The rapid emergence and spread of Multi-drug Antimicrobial Resistance (AMR), alongside the negligible efforts of the major pharmaceuticals companies in the development of new antibiotics, result in a major global concern of modern medicine. Moreover, the currently clinically used antibiotics contaminate the environment and may harm the human microbiome, causing unpredictable health concerns. We discovered that by targeting species-specific ribosome unique structural motifs, identified by us, using our designed degradable novel synthetic lead compounds, it is possible to inhibit protein biosynthesis in bacteria. Our approach should enable distinction between pathogenic and non-pathogenic bacteria and between bacterial and human ribosome. This drug selectivity should decrease resistance, preserve the beneficial microbiome and allow usage of lower antibiotics dozes. Furthermore, the designed degradable lead compounds should prevent additional environmental contamination. Hence, our approach allows designing innovative powerful selective antibiotics that escape the existing resistance mechanisms. Several of the primary designed compounds shown to stop the growth of the multi-resistant S. aureus human pathogen were delivered into the bacterial cells by attaching specific chemical moieties to them. In this PoC we plan to design similar compounds for other human pathogens, such as Enterococcus and Pseudomonas species, where revolutionary effective antibiotic drugs against their resistant strains is desperately needed. In addition to the technological PoC in this project, we will attempt pre-commercialization studies aiming at perfecting the commercialization strategy, protecting the IP and strengthen the network for best possible commercialization outcome. The general objective is to establish at least one strategic partnership with a pharma company which has the capacity to further test, develop and commercialize antibiotics that exploit ribosomal novel unique targets.
Champ scientifique
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Mots‑clés
Programme(s)
Régime de financement
ERC-POC - Proof of Concept GrantInstitution d’accueil
7610001 Rehovot
Israël