The McPhee lab studies the behaviour of numerous intestinal bacteria, particularly those associated with food and water borne diseases like E. coli, Shigella and Salmonella and enteric bacteria associated with inflammatory bowel diseases, like 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:

1. 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.
2. 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.
3. Regulation of bacterial morphology and the contribution of morphological changes to host-pathogen interaction. During infection, many bacteria undergo profound morphological changes. This is especially true during the life cycle of uropathogenic E. coli, the lead cause of urinary tract infections around the world. During infection, UPEC will stop dividing and undergo a dramatic transition to a filamentous morphology and in this project we seek to understand how this change affects interactions with the host immune system.
4. Gene loss as a driver of virulence in Shigella spp. Shigella have evolved on multiple occasions when an E. coli bacterium acquired a virulence plasmid that enabled a new type of intracellular lifestyle. Since that acquisition, bacteria that became Shigella have continued to acquire and lose genes from their genome. This project focuses on how loss of bacterial signaling systems have altered the behaviour of Shigella spp bacteria.