Project 461872

Antibiotic resistance is a process where disease-causing bacteria acquire or evolve strategies to evade the drug's killing activity. Interventions ranging from the treatment of pneumonia to cancer chemotherapy rely on antibiotics to overcome and prevent infection. Antibiotic resistance is a pandemic; it is a global infectious disease threat that kills 5,400 Canadians and drains over $2 B in lost wealth to our economy per year. The COVID-19 pandemic has shown how important it is to control infectious diseases and what the consequences are when we cannot. Work in my lab focuses on understanding mechanisms of antibiotic resistance, where resistance comes from, how it spreads between bacteria and across the globe, and how we can overcome it. In this project, we propose to build on the extensive experience and unique resources developed over many years in my group. Examples include a library of antibiotic resistance gene-expressing bacteria, clinical isolates of multi-drug resistant bacteria, and a unique collection of bacteria and fungi that produce compounds that can block antibiotic resistance. We will use these resources to explore new mechanisms of resistance emerging both in the clinic and in the environment, the source of most resistance genes. By understanding the molecular details of resistance, we are better prepared to overcome it. A second complementary element of this project is the testing and discovery of molecules that can block resistance. The pairing of existing antibiotics threatened by resistance with such inhibitory molecules can extend the life of our 'old' antibiotics that have proven to be so vital to our health and economy. Outcomes of this work include new knowledge of resistance, new candidate molecules that can block resistance, the training of scientists and clinicians with a profound understanding of the antibiotic resistance crisis, and ultimately new drug candidates to address this existential threat to modern medicine.