Natural Product-Inspired Approaches to Combat Bacteria

The overarching goal of the Wuest research group is to utilize chemical biology to better understand bacterial processes. Initially the group focused on tackling bacterial biofilms  as they are ubiquitous with an estimated to cost society in excess of $200 billion/yr, affecting everything from human health to water purification. Furthermore, biofilms are increasingly resistant to antibiotic treatment and are responsible for persistent infections. Most recently, we have switched our attention to developing narrow-spectrum agents and using chemical probes to learn more about resistance mechanisms. Our group implements a variety of methods to interrogate these process with the overarching goal of identifying novel treatments and new targets for pharmaceutical development. Nationally, only a few synthetic endeavors have approached this problem in a similar way thus positioning our group for therapeutic breakthroughs.

Currently, we are pursuing a number of synthetic projects targeting natural products with unknown mechanisms of action that target bacteria. In conjunction, we are also using microbiological and biochemical approaches to discover new therapeutics, identify unprecedented biological targets, and test the efficacy of compounds developed in house. The goal of each of these projects is to make chemical analogs to test biological hypotheses. Typically this involves constructing compounds that mimic the natural products but are simpler and more “drug-like” thus possessing better pharmacokinetic properties thereby maximizing the likelihood of success of therapeutic development. The group is highly interdisciplinary and has key collaborations throughout the world (Cornell, TU-Munich, Villanova, Rochester) and also at Emory (Antibiotic Resistance Center, Cystic Fibrosis-Atlanta) expediting the testing of compounds and evaluation of their mechanism of action.