Grant: Doctoral Research Award: Canada Graduate Scholarships

Antimicrobial resistance (AMR) is a growing crisis, with projections suggesting it could cause 396,000 deaths and cost $388 billion by 2050, placing a severe strain on healthcare systems and economies. A key factor driving AMR is the presence of beta-lactamase enzymes, which can break down important antibiotics and spread from environmental microbes to harmful human pathogens. These enzymes are highly diverse, and their wide-ranging abilities make it difficult to predict and control resistance. Traditionally, research has focused on a limited number of beta-lactamases characterized in lab strains (E. coli), leaving many potentially dangerous sequences overlooked. To address this, my research aims to expand our understanding of these enzymes by sampling and characterizing a broad range of unexplored sequences. By examining thousands of new beta-lactamases from various classes and testing their effects against different antibiotics, I will uncover patterns that reveal how these enzymes work and spread. This involves creating and testing large libraries of beta-lactamase genes, using advanced synthesis techniques and characterization assays to measure how effectively each gene confers resistance. In particular, I will explore how these enzymes behave in different clinical bacterial hosts to assess their potential to spread in clinical settings. This will help identify which beta-lactamases pose the highest risk of dissemination. Additionally, I will analyze the sequence data to predict future beta-lactamases that could become significant in resistance, using sophisticated modeling techniques to identify key features and evolutionary trends. This study will significantly enhance our knowledge of beta-lactamases by vastly increasing the number of characterized enzymes and improving our ability to predict future resistance threats. These insights will be crucial for developing new antibiotics and strategies to manage AMR, ultimately helping to safeguard public health.