Oligomannose-Rich Membranes of Dying Intestinal Epithelial Cells Promote Host Colonization by Adherent-Invasive E....

Area of Science:

• Microbiology and Immunology
• Gastroenterology
• Cell Biology

Background:

• Adherent-invasive Escherichia coli (AIEC) is implicated in Crohn's disease pathogenesis.
• The precise mechanisms of AIEC invasion and colonization of the intestinal epithelium remain incompletely understood.
• Host cell surface glycans are critical for bacterial adhesion and invasion.

Purpose of the Study:

• To elucidate the novel mechanism by which AIEC penetrates the epithelial cell layer.
• To identify specific host cell targets and bacterial factors involved in AIEC colonization.
• To investigate the role of CEACAM6 in AIEC-host cell interactions.

Main Methods:

• Analysis of clinical AIEC isolates.
• Investigation of bacterial binding to host cells using FimH adhesin and oligomannose glycans.
• Demonstration of oligomannosylation on CEACAM6 using Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS).

Main Results:

• AIEC preferentially binds to oligomannose glycans on early apoptotic host cells, utilizing them as entry points.
• AIEC replicates within epithelial intercellular spaces and establishes biofilms.
• Oligomannosylation, specifically oligomannose-5, was identified on CEACAM6, serving as a high-affinity binding site for FimH.

Conclusions:

• AIEC employs a novel mechanism involving FimH-mediated binding to oligomannose on apoptotic cells and CEACAM6 for epithelial invasion.
• This interaction facilitates AIEC colonization and biofilm formation, contributing to Crohn's disease.
• The identified mechanism may be relevant for other mannose-dependent infections by adherent-invasive pathogens.