Titre du projet
Mfd profiling
Nom de l'appel d'offre
TWB 2019
Gwenaëlle andré-Leroux (INRA, MaIAGE) et Nalini Rama Rao (INRA, Micalis)
Participants de MaIAGE
Gwenaëlle andré-Leroux
Partenaires (hors MaIAGE)
Année de démarrage - Année de fin de projet
Date de fin du projet
The search for new antimicrobials is an urgent health issue. We have identified a bacterial protein as an innovative target for the development of new drugs. We performed a high throughput in silico screening to select molecules specifically binding to the active site of the target while blocking bacterial resistance to the host immune stress. we showed that the hits are efficient in vitro and efficient and non-toxic in vivo, in an insect model of infection on at least two bacterial pathogens. These preliminary data constitute a proof of concept of the innovative potential of our hits. We now aim to assess their antibacterial efficacy in a mammalian model of infection as well as their innocuity for the host. In parallel, we want to model their molecular mode of action, including their accessibility and their specific binding to the target, to be able, after QSAR analysis, to chemically optimize those compounds. The protein associates a complex functional cycle with distinct conformations at each step of the cycle that need to be described to enhance its specific inhibition. By the end of the project, our first objective is to obtain at least one preclinical candidate with high therapeutic potential. The second one is to capitalize on the combination of technologies developed in this project to potentiate this protein target in biotechnological applications, such as its use in the limitation of bacterial contaminations in fermentation processes.
Année de soumission