Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

According to the Centers for Disease Control and Prevention, diarrheal disease claims the life of 1 in every 10 children under the age of 5 - that is 800,000 children worldwide each year. The bulk of diarrheal illness is caused by fecal contamination by a group of bacteria called attaching and effacing (A/E) pathogens. A/E pathogens are a major threat to food and water safety in Canada, with an estimated annual cost of $403.9 million to the economy. To establish an infection, A/E pathogens must overcome many environmental barriers including the host immune system and the trillions of microorganisms (such as bacteria, viruses, parasites, and fungi) inhabiting a healthy gut. Recent studies indicate that a 'bottleneck' effect occurs during colonization of A/E pathogens, restricting the sheer number of individual bacteria able to establish a foot hold in the intestine, and effectively decreasing the genetic diversity of the population. For example, in a study using individually tagged Citrobacter rodentium, a mouse A/E pathogen, only half of the tags remained within the population after infection despite equal fitness of the bacteria. The cause of these bottlenecks remains unknown. My research will focus on characterizing the population dynamics of C. rodentium as infection progresses, and on identifying factors affecting bottlenecks across intestinal regions, at different time points post infection. We hypothesize that bottlenecks are caused by a combination of factors from both the host and microbiota such as intestinal integrity and nutrient availability, or chemical signals released by resident microbes. I will then go on to manipulate these factors for their ability to cause bottlenecks. This research is important to help us understand the tripartite interactions between the host, pathogen, and microbiota which influence bacterial infection in the hopes of developing novel therapeutics to combat the rise in antibiotic resistance.