Grant: Project Grant

Antimicrobial resistance is a grave threat to human health. The Council of Canadian Academies report "When Antibiotics Fail" (2019) predicted that by 2050, antimicrobial resistance will cause the death of 256,000 Canadian lives and cost our healthcare system $7.6 billion annually. The emergence of drug-resistant infections highlights a critical need for new antimicrobials. Current antibiotics and the human immune system cause severe damage to bacterial DNA in an effort to eradicate the infection, however bacteria maintain DNA repair pathways fix the damage. These bacterial DNA repair systems not only prevent bacterial death, but can lead to mutations that result in antibiotic resistance. Therefore, inhibiting bacterial DNA repair pathways is a potential source of new therapeutic targets. However, to achieve this aim a detailed understanding of the mechanisms of bacterial DNA repair are required. The goal of the proposed research is to unravel the molecular mechanisms of a bacterial DNA repair pathway that fixes the most lethal form of DNA damage - the double-strand break. We will use structural and biochemical methods to find the critical features of the protein complex that repair DNA. The foundational knowledge provided by this research will highlight new drug targets for the development of innovative antimicrobials to combat infectious disease.