Grant: Project Grant - PA: Antimicrobial Resistance (Bridge Grant)

Antibiotics are used to treat bacterial infections and are a critical part of healthcare in Canada and worldwide. Unfortunately, bacteria are, more and more frequently, becoming resistant to the antibiotics we have, which weakens the effectiveness of antibiotics and healthcare as a whole. Bacteria have developed several ways of dealing with antibiotics including several different Multidrug Efflux Pumps, which can remove antibiotics from bacteria, and assist in the emergence of antibiotic-resistant infections. If we were able to disable these efflux pumps with new drugs (pump inhibitors), many resistant bacteria would once again be treatable by antibiotics we already have, and we could help to slow the emergence of new resistant bacteria. This project will investigate efflux pumps from bacteria that are often found in resistant infections (Acinetobacter baumannii), which is among the top three priority pathogens for discovery, research, and development of new antibiotics. We aim to understand how these pumps work and to identify regions of the pump that could be targeted by pump inhibitors. We are particularly interested in parts of the pump that are similar among many different efflux pumps, because targeting these with efflux pump inhibitors will provide a good chance of disabling multiple pumps simultaneously. This project will use high-precision (fluorescence-based) experiments to examine pump activity in real time to help us understand how fast the pumps can assemble and operate. This will lay the foundation for discovery of drugs that can slow down the efflux pumps and impact antibiotic resistance.