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

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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., Augustin, C., Fromm, A., Piontek, A., Walther, W., Buecker, R., Fromm, M., Krause, G., Schulzke, J.D., 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
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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