Grant: Project Grant

Antimicrobial resistance is one of the biggest health, economic and security threats to mankind. Without more effective therapies, it is estimated that 10 million people will die from previously treatable infections by 2050. New therapeutic options are urgently needed, yet antibiotic development has stalled. This proposal seeks to comprehensively characterize bacterial energetic systems, a relatively unexplored antibiotic target, in order to discover, design and optimize more effective antibiotic therapies for multidrug-resistant pathogens. We, and others, have recently revealed that clinical drugs for conditions such as heart disease and diabetes can be repurposed as antibiotics due to their effects on bacterial energetics. In this proposal, we will systematically explore the mechanisms through which these drugs disrupt bacterial energy systems, and examine the ways through which resistance could evolve against them. Furthermore, we will examine the antibiotic efficacy of these drugs in in vitro and in vivo infection models to validate their potential as effective clinical therapies. With promising preliminary results to date, our proposal provides a realistic and feasible path toward the development of new therapeutic options for bacterial infections. The FDA-approved status of these drugs, the protection of intellectual property, and current negotiations with commercial partners, offers promise for rapid progression into the clinic, which is urgently needed to combat this global emergency.