Grant: Project Grant

Bacteria are now defined by both their ability to cause disease and to resist antibiotics. In fact, antimicrobial resistance (AMR) has been identified as the cause of a growing pandemic. While we are now too familiar with the definition and impact of a global viral pandemic, that being caused by AMR is the result of widespread failures of antibiotic treatments. Unfortunately, this is a multifactorial public health crisis: many bacteria possess many antimicrobial resistance genes that undermine the action of once life-saving drugs. In 2019, the number of deaths attributed to AMR was estimated at nearly 1.3 million people worldwide. Unfortunately, our knowledge of clinically relevant resistance genes is incomplete and the pool of genes contributing to high rates of mortality is dynamic. Thus, research that is aimed to identify and understand currently unrecognized mechanisms of resistance is essential to our fight against infectious disease. Our group is particularly interested in bacterial enzymes that inactivate antibiotics. Overall, our goals encompass identification and characterization of genes that contribute to resistance but that have been overlooked. We will use a holistic One Health approach that spans human and veterinary medicine and that incorporates publicly available genome datasets from around the world. Enzymes that we assign new roles in AMR will be characterized and compared to each other. An integrative enzyme research program will implement molecular, biochemical and biophysical methods to study how these have evolved and how they may change in the face of continued natural selection imposed by antibiotics. A better understanding of how enzymes that inactivate antibiotics work will help to inform future antimicrobial use and innovation.