New Targets, New Tools: Advancing the Fight Against Antimicrobial Resistance

One method for overcoming current bacterial resistance mechanisms is to explore new biochemical targets involved in essential cellular processes, however there are many challenges in developing bioenergetic targeting antibiotics for GN pathogens. Amanda Wolfe of UNC at Asheville will discuss how to overcome some of these challenges based on recent advances in the field and discuss the future of GN antibiotic discovery.

Combatting resistance does not solely depend on continuous development of new antibiotic rather a combined effort of understanding the molecular mechanisms of resistance and repurposing molecular scaffolds to resensitize pathogens. Ruchi Anand of the ITT in Bombay, India has used structural biology approaches and extensive biochemical techniques in order to highlighted subtle recognition elements in both the protein as well as the in vitro and in vivo enzyme substrate that govern their interaction and lead to effective catalysis. She will discuss how her and her team helped to uncover a unique universal dual base flipping mechanism employed by Erms and created novel drug scaffolds that show promising results against Erm-containing microbes, thereby curbing methylation-based resistance in pathogens.

GN bacteria have the ability to sense the damage inflicted to their cell wall by B-lactam antibiotics. The process involves chemical signaling and a primary mechanism for this sensing and signaling involves the events of cell-wall recycling. GN bacteria like Pseudomonas aeruginosa recycle their damaged cell walls, triggered by a family of 11 lytic transglycosylases, to generate signals that activate repair pathways. Shahriar Mobashery of the University of Notre Dame will explore the mechanisms of these processes as well as strategies aimed at interrupting this recycling process as a means of weakening bacterial resistance.

This ACS Webinar is moderated by Greg Basarab of University of Cape Town in South Africa and is co-produced by ACS Publications.