Canada has one of the world’s highest rates of inflammatory bowel disease (IBD) and newly diagnosed Crohn’s disease (CD) incidence has doubled since 1995. The intestinal bacterial composition of CD patients is altered compared to healthy controls, principally due to the expansion of adherent-invasive Escherichia coli (AIEC). The McPhee lab studies the behaviour of Crohn’s disease-associated E. coli (AIEC) to understand how this group of bacteria induces and adapts to the inflammatory conditions associated with the disease. By utilizing comparative genomic, molecular biological, microbiological, biochemical and immunological techniques, we seek to define the molecular determinants of bacterial fitness under pro-inflammatory conditions.
Projects available include, but are not limited to, the following:
- Regulation and function of outer membrane proteases in enteric bacteria. Bacteria have evolved complex regulatory systems to combat the host antimicrobial activity. Among these responses are outer membrane embedded proteases that can degrade host defense peptides. We seek to understand both how these are regulated and how different proteins contribute to bacterial behaviour.
- Regulation and essentiality of AIEC-enriched metabolic pathways. Unlike other pathovars of coli, the genetic diversity in AIEC is particularly broad. As little is known about which genes/pathways are important for fitness in AIEC, this project will consist of identifying novel genes in clinical AIEC isolates, creating deletions of these genes for phenotypic characterization of the associated mutants as well as creating translational fusions to the promoters of these genes to determine whether and how these genes are regulated.
- Heterogeneity in bacterial signaling systems. Bacteria have conserved two-component regulatory systems and these systems play a crucial role in how bacteria respond to different environments, including virulence. Different strains of the same bacteria can have very different behaviour in response to identical conditions. We seek to characterize these differences as well as understand the effects it has on bacterial behaviour.
- Regulation of bacterial morphology and the contribution of morphological changes to host-pathogen interaction.
- Gene loss as a driver of virulence in Shigella spp.