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In colon epithelia, Clostridium perfringens enterotoxin causes focal leaks by targeting claudins which are apically accessible due to tight junction derangement

Item Type:Article
Title:In colon epithelia, Clostridium perfringens enterotoxin causes focal leaks by targeting claudins which are apically accessible due to tight junction derangement
Creators Name:Eichner, M. and Augustin, C. and Fromm, A. and Piontek, A. and Walther, W. and Buecker, R. and Fromm, M. and Krause, G. and Schulzke, J.D. and Guenzel, D. and Piontek, J.
Abstract:Clostridium perfringens enterotoxin (CPE) causes food poisoning and antibiotic-associated diarrhea. It uses some claudin tight junction proteins (e.g. claudin-4) as receptors to form Ca(2+)-permeable pores in the membrane damaging epithelial cells in small intestine and colon. We demonstrate that only a subpopulation of colonic enterocytes which are characterized by apical dislocation of claudins are CPE-susceptible. CPE-mediated damage was enhanced if paracellular barrier was impaired by Ca(2+)-depletion, proinflammatory cytokine TNF{alpha} or dedifferentiation. Microscopy, Ca(2+)-monitoring, and electrophysiological data showed that CPE-mediated cytotoxicity and barrier disruption was limited by extent of CPE-binding. The latter was restricted by accessibility of non-junctional claudin molecules such as claudin-4 at apical membranes. Focal-leaks detected in HT-29/B6 colonic monolayers were verified for native tissue using colon biopsies. These mechanistic findings indicate how CPE-mediated effects may turn from self-limiting diarrhea into severe clinical manifestation such as colonic necrosis - if intestinal barrier dysfunction e.g. during inflammation facilitates claudin accessibility.
Keywords:Claudin, Clostridium perfringens Exterotoxin, HT-29/B6 Cells, Pore-Forming Toxin, Tight Junction
Source:Journal of Infectious Diseases
ISSN:0022-1899
Publisher:Oxford University Press (U.K.)
Volume:217
Number:1
Page Range:147-157
Date:27 December 2017
Official Publication:https://doi.org/10.1093/infdis/jix485
PubMed:View item in PubMed

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