L'integration de la bioinformatique structurelle et la biologie des systèmes dans la recherche de nouvelles antibiotiques ciblant C. difficile

 

Rafael Najmanovich

Université de Sherbrooke

 

Domaine : maladies infectieuses et immunitaires

Programme chercheurs-boursiers - Junior 2

Concours 2016-2017

C. difficile is a spore forming bacteria that causes mild to severe diarrhea and colitis. C. difficile infections are of particular importance in health care settings upon depletion of the normal intestinal flora following antibiotic administration. CDI and relapses can be fatal for the elderly as well as those with other illnesses and are a major burden to the health care system. A major problem in fighting C. difficile infections is the resistance of the spores to heat and other treatments. One particular protein in C. difficile plays a fundamental role in the germination of spores. Without this protein C. difficile spores take much longer to germinate.

The goal of this research is to employ a number of computational methods to detect inhibitors for this protein as well as others that may be potential new therapeutic targets for future antibiotics. Our computational methods aim at identifying molecules that will strongly bind to these targets at the same time that they do not interact with proteins in other bacteria that are present in the healthy intestinal flora as well as human proteins. The prevention of binding to other proteins is to ensure that at the same time that we fight a C. difficile infection, we do not prevent the reestablishment of the healthy intestinal microbial flora or causes side-effects in human cells.

All molecules that are identified computationally will be validated experimentally, molecularly, in growth and germination assays as well as in mice models of C. difficile infections. The integration of computational and experimental methods lies at the forefront of biological research and help integrate all our knowledge of C. difficile biology.