Interactions between adherent-invasive Escherichia coli and host macrophages: a virulence phenotype.
thesisposted on 21.05.2021, 12:12 by Michael John Dill Renouf
Inflammatory bowel disease (IBD) is a chronic condition increasing in prevalence throughout the western world and in developing countries. Adherent-invasive Escherichia coli (AIEC) are an opportunistic pathogen associated with IBD. Well-characterized genetic risk factors for IBD include mutations in genes associated with host-cell autophagy. A phenotype of interest in AIEC pathogenesis is survival within host macrophages. Intracellular survival of AIEC strains has been correlated with existing virulence factors but no single factor has been identified to explain this behaviour. In this thesis, infections of RAW264.7 macrophages with AIEC strains from diverse sources demonstrates increased frequency of both bacterial uptake and intracellular survival in disease-associated strains. A secondary infection model reveals the effect of primary AIEC infection on downstream macrophage function and a novel phenotype was identified in the disease-associated strain HM605. Co-localization using fluorescence microscopy shows changes in intracellular trafficking of HM605. This work aims to provide insight into one bacterial phenotype that contributes to the development of disease