Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Over 6 million people are affected by Crohn's disease (CD) worldwide. CD is a chronic inflammatory bowel disease marked by an abnormal immune response to gut bacteria. While the exact cause remains unknown, adherent-invasive strains of Escherichia coli (AIEC) are frequently isolated from CD patients. These bacteria are able to trigger inflammation in mouse models, making it critical to understand their role in exacerbating intestinal damage. Previous work has highlighted the importance of the type IV secretion system (T4SS) as an important factor that allows for AIEC to persist in the gut. The T4SS is a complex protein structure that spans across the bacterial cell wall to carry out a variety of functions. Though best characterized for their role in facilitating DNA transfer between bacteria, T4SSs can also mediate the formation of biofilms. These are protective matrices of sugars, DNA, and proteins secreted by bacteria to shield against antibiotic killing and other stresses. Our preliminary work has uncovered a previously unknown hybrid T4SS in a CD-associated AIEC strain that promotes disease and persistence of the bacteria in the gut. Moreover, we found that this biofilm-forming AIEC strain resists killing by immune cells, while a biofilm-deficient mutant is eradicated. However, the mechanisms by which these bacteria contribute to greater inflammation remain unclear. The proposed research will investigate how specific components of these biofilm structures protect AIEC from killing by immune cells with the goal of translating these findings to patient biopsy samples. Ultimately, this work will advance our understanding of how bacterial biofilms resist killing and will guide the development of new therapies and diagnostic methods for CD.