HKI Kolloquium

Targeting bacterial toxins as antibiotic alternative in the fight against Clostridium difficile infection

Prof. Dr. Bastien Castagner

McGill University, Montreal, Canada

Abstract:

Clostridium difficile infection continues to cause significant morbidity and mortality despite efforts to develop novel therapies. The TcdB toxin secreted by the bacterium has emerged as an interesting target for therapeutic antibody, but as of yet, no small molecule has reached clinical trials. We report a rational approach designed to irreversibly inactivate the bacterial toxin by prematurely triggering its auto-proteolysis. We modulated the physico-chemical properties of an essential co-factor in the pathogenesis of TcdB in order to obtain oral small-molecule drug candidates. We demonstrated the potential of this approach in two animal infection models. Our findings are highly relevant to the ongoing pursuit of novel anti-infective strategies that are not based on antibiotic and provide impetus for further investigating toxin auto-processing as a therapeutic approach.

Bio:

Bastien Castagner obtained a Ph.D. in Chemistry at Columbia University in New York in 2004. His postdoctoral years were spent at ETH Zürich from 2005 - 2008. From 2009 - 2014 he was a Group Leader in the Institute of Pharmaceutical Sciences at ETH Zürich. He joined the Department of Pharmacology & Therapeutics at McGill, as Assistant Professor, in August 2014.
Dr. Castagner’s research focuses on the design of small-molecules and natural product analogues as novel drug candidates. He is especially interested in the chemistry and biology of inositol phosphates. His group has also been involved in novel strategies to inactivate the toxins responsible for the pathogenesis of Clostridium difficile. He is also pursuing the modulation of the gut microbiota composition.