Dr Julie McDonald
ISSF Springboard Fellowship
Investigating the mechanism of intestinal decolonisation of multidrug-resistant opportunistic pathogens using faecal microbiota transplantation
Antimicrobial resistant (AMR) infections are a serious threat to human health, resulting in treatment failures, infection relapses, longer hospitalizations, and poor clinical outcomes. The intestine is the primary colonisation site for AMR pathogens and serves as a reservoir for bacteria responsible for infections (e.g. sepsis and urinary tract infections). Stool transplants can decolonise AMR pathogens from the intestine, however the mechanism of stool transplants is unknown, and there are several drawbacks to administering stool transplants to these patients. Stool transplants need to be replaced with safer, more effective therapies.
The aim of my research program is to determine the mechanism for the intestinal decolonisation of AMR pathogens using stool transplants, with the goal to identify a microbial metabolite, microbial enzyme, bacteria, or bacteriophage that can inhibit AMR pathogen growth in the intestine. In this study I demonstrated the successful colonisation of AMR pathogens in an artificial gut model (aka “Robogut” model) designed to mimic the guts of patients with intestinal AMR pathogen colonisation. I also demonstrated a significant decrease in the growth of AMR pathogens in response to stool transplants using this artificial gut model. This research program will directly impact clinical practice by developing a novel method for AMR pathogen intestinal decolonisation that is rationally-designed, effective, safe, and doseable.
Dr Eleanor Sandhu is an Imperial Post-CCT, Post-doctoral Research Fellow and Honorary Consultant Nephrologist at Imperial College Healthcare NHS Trust. As a Chain Florey Fellow, she undertook a PhD investigating the role of ventral tegmental area dopamine neurons in salt appetite. Her research now focuses on the neurobiology of the body-brain axis in modifying salt intake and its translation to the clinical care of renal patients.