Grant: Project Grant

Intestinal infection with bacterial pathogens is a major cause of illness, hospitalization, and death, around the world. Food-borne bacterial pathogens can cause food poisoning (gastroenteritis), with symptoms including abdominal cramps, diarrhea, and vomiting. Further, bacterial infection is a potential trigger of inflammatory bowel disease, and a known cause of disease relapse. To identify those at the greatest risk of bacterial infection, and design preventative treatment strategies, it is important to understand the basis of susceptibility to infection. Our intestines have several defence mechanisms to prevent infection with bacterial pathogens. Our immune system can kill or force the expulsion of invading bacteria. Further defence is provided by the thousands of species of non-harmful bacteria that under normal circumstances live in our intestines (the microbiota). Our intestinal microbiota help to prevent infection with bacterial pathogens by competing with them for space and nutrients and by stimulating our intestinal immune defences. Our research uses mouse infection models to understand how disruptions to the intestinal immune system and microbiota can influence susceptibility to pathogenic bacterial infection. We have shown that mice infected with intestinal parasitic worms are highly susceptible to intestinal infection with pathogenic bacteria. This provides us with an excellent model system for understanding how an altered intestinal environment can result in susceptibility to bacterial infection. We will investigate how altered immune activation and disruption of the microbiota during parasitic worm infection alters the ability of pathogenic bacteria to infect the intestine. We expect that our work will contribute to strategies to control bacterial-driven intestinal disease, including gastroenteritis and inflammatory bowel disease, as well as predicting and controlling the adverse effects of parasitic worm infection.