DrJulie McDonald, PhD

The human gut is colonised by a diverse microbial community collectively referred to as the gut microbiota. A healthy gut microbiota provides protection against intestinal colonisation by pathogens, however disruption of the gut microbiota can weaken colonisation resistance (e.g. following exposure to antibiotics), increasing the host’s susceptibility to the intestinal colonisation with pathogens and the subsequent development of difficult to treat invasive infections. The aim of our research is to develop novel microbiome therapeutics to restore microbiota-mediated colonisation resistance and decolonise multidrug-resistant pathogens from the intestine.

Antimicrobial resistance is 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 multidrug-resistant organisms (MDROs) and serves as a reservoir for MDROs that are responsible for invasive infections (e.g. sepsis and recurrent urinary tract infections). Antibiotic treatment makes the host more susceptible to intestinal colonisation with pathogens such as carbapenem-resistant Enterobacteriaceae (CRE), vancomycin-resistant Enterococcus (VRE), and other multidrug-resistant pathogens that we are investigating in our lab. The goal of our research is to determine the mechanism(s) by which gut microbiota-mediated colonisation resistance protects the host against intestinal MDRO colonisation, with the aim to develop a new microbiome therapeutic for MDRO intestinal decolonisation. We are particularly interested in gut microbiota-mediated nutrient competition and metabolite inhibition.

Our lab uses a variety of complementary approaches to study gut colonisation resistance, including artificial gut models (aka “chemostat” or “Robogut” models), batch culture experiments, and human faecal samples. Samples are analysed using both culture-dependent and culture-independent techniques, including a variety of “omic” techniques (e.g. 16S rRNA gene sequencing, 1H-NMR spectroscopy, and mass spectrometry).