Interaction of Shiga toxin from Escherichia coli with human intestinal epithelial cell lines and explants: Stx2 induces epithelial damage in organ culture

Schuller, Stephanie ORCID: https://orcid.org/0000-0003-3260-9112, Frankel, Gad and Phillips, Alan D. (2004) Interaction of Shiga toxin from Escherichia coli with human intestinal epithelial cell lines and explants: Stx2 induces epithelial damage in organ culture. Cellular Microbiology, 6 (3). pp. 289-301. ISSN 1462-5814

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Abstract

Shiga toxins (Stx) produced by Escherichia coli are associated with systemic complications such as haemolytic–uraemic syndrome. The mechanism of Stx translocation across the epithelial barrier is unknown as human intestinal epithelium lacks receptor Gb3. In this study, we have examined the interaction of purified Stx1 and 2 with Caco-2 (Gb3+) and T84 (Gb3–) cell lines, and determined the effects of Stx on human intestine using in vitro organ culture (IVOC). Stx exposure caused inhibition of protein synthesis and apoptosis in Caco-2 but not in T84 cells. However, both Stx1 and 2 were transported to the endoplasmic reticulum, and the Stx1 A-subunit was cleaved in a furin-dependent manner in both cell lines. Thus, a Gb3-independent retrograde transport route exists in T84 cells for Stx that does not induce cell damage. IVOC demonstrated increased epithelial cell extrusion in response to exposure to Stx2, but not Stx1, in both small intestine and colon. Pretreatment of Stx2 with Stx2-specific antibody abrogated this effect. Overlaying frozen sections with Stx showed lamina propria, but not epithelial, cell binding that paralleled Gb3 localization, and included endothelium and pericryptal myofibroblasts. This indicates that human intestinal epithelium may evince Stx2-induced damage in the absence of Gb3 receptors, by an as yet unrecognized mechanism.

Item Type:	Article
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Pathogen Biology Group
Depositing User:	Rhiannon Harvey
Date Deposited:	20 Jul 2011 09:44
Last Modified:	24 Sep 2024 10:02
URI:	https://ueaeprints.uea.ac.uk/id/eprint/33962
DOI:	10.1046/j.1462-5822.2004.00370.x

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