Monitoring epithelial cell responses to an IBD-associated bacterial pathotype using quantitative proteomics (P1352)

Abstract

Abstract Many lines of evidence suggest that the initiation of inflammatory bowel disease (IBD) involves abnormal host-microbial interactions at the intestinal epithelium. One microorganism that is commonly associated with the intestinal mucosa of IBD patients but not from healthy subjects is called adherent invasive E. coli (AIEC). AIEC are a new pathotype defined by their ability to adhere to and invade epithelial cells in the absence of known virulence factors associated with other pathogenic E. coli. Previous work has demonstrated that AIEC infection of epithelial cells induces cell-intrinsic responses such as the activation of autophagy markers, reduction of barrier function and secretion of IL-8. However, a comprehensive analysis of the cellular response to AIEC has not been performed. Here, we take a global approach to define how protein levels are altered in epithelial cells exposed to AIEC using quantitative mass spectrometry. This experimental strategy allows us to determine how the endogenous abundance of known and novel cellular proteins is altered by AIEC infection. Our preliminary results reveal specific differences between the epithelial cell response to adherent invasive E. coli compared to commensal E. coli not associated with IBD. Ongoing work examines whether any of the changes in protein abundance observed in response to AIEC infection are necessary for AIEC attachment, invasion, or intracellular growth.