Join a panel of experts in celebration of World Antimicrobial Resistance Awareness Week, that will not only raise awareness of today’s challenges, but will discuss advances in structural biology, biochemical methods, and drug design that are converging to provide unprecedented insights into multi-drug resistant mechanisms (MDR) and pathways in Gram-negative (GN) bacteria.
MDR bacteria are linked to 5.85 million deaths worldwide, with infections from harder-to-treat GN bacteria rising sharply over the past 30 years due to their extra outer membrane. 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 University of North Carolina 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 Indian Institute of Technology (IIT) 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 β-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 independent contractor Greg Basarab and is co-produced by ACS Publications.
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What You Will Learn
- Why bioenergetics are a viable target for antibiotic development in Gram-negative bacteria
- How to selectively inhibit ATP synthase in Pseudomonas aeruginosa and Acinetobacter baumannii
- What to consider when targeting the electron transport chain
- What is methylation based ribosomal modification and its role in antimicrobial resistance
- How allostery is involved in target recognition and how to decipher novel druggable sites for a structure guided approach
- How the development of peptide conjugate antibiotic scaffolds can reverse resistance
- What are the mechanisms of antibiotic action and how do they work
- The mechanism of cell-wall recycling for a damaged cell wall
- What are some strategies in adjuvant development for enhancement of activities of ß-lactam antibiotics
Additional Resources
- Raising Antimicrobial Awareness Virtual Issue - ACS Publications presents this Virtual issue highlighting important research and advances made in the field over the last few years. Click on the link to be inspired by the various efforts featured in these articles to identify novel antimicrobials and to combat antimicrobial resistance!
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