Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Antimicrobial resistant (AMR) pathogens are an ever-growing health threat associated with an estimated five million deaths in 2020, projected to reach ten million by 2050. The development of new antibiotics is a slow and expensive process. Drugs typically target conserved processes under strong selective pressure, meaning bacteria can rapidly develop and share mutations conferring resistance. Even new antibiotics may quickly become vulnerable to widespread resistance, emphasising the need for novel mechanisms of action. Many highest-risk AMR pathogens infect the gut, where they encounter the community of bacteria, yeast, and viruses known as the gut microbiota. Bacterial members can confer resistance to pathogen infection through a multitude of mechanisms: secreting toxic compounds, outcompeting pathogens for nutrients, and even killing cells with direct physical interaction. This project proposes to use such gut microbes as live biotherapeutics to target classically resistant and recalcitrant bacterial pathogens, as well as future potential pandemic strains. My aim is to utilize high-throughput screens of the human gut microbiota - collected from a diverse array of healthy volunteers - to identify and characterize for bacteria that defeat (i.e., exclude and/or eradicate) gastrointestinal pathogens. In brief, I will identify human-isolated bacteria that can defeat a common gut pathogen - Salmonella - in one-on-one and complex community competition, both in the lab and in animal models. I will then work to understand the mechanisms by which these strains succeed, and explore their potential as either prophylactic or reactionary treatment to disease. This project will develop and validate a robust framework for future screens against emerging pandemic-level pathogen threats. By screening the highly diverse gut microbiota, we will diversify both mechanisms and targets, providing an alternative to the classical antibiotic drug discovery approach.