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Clostridium perfringens Delta-Toxin Damages the Mouse Small Intestine

Laboratory of Molecular Microbiological Science, Faculty of Pharmaceutical Sciences, Hiroshima International University, Kure, Hiroshima 737-0112, Japan
Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan
Author to whom correspondence should be addressed.
Received: 27 March 2019 / Revised: 8 April 2019 / Accepted: 17 April 2019 / Published: 22 April 2019
Clostridium perfringens strains B and C cause fatal intestinal diseases in animals. The secreted pore-forming toxin delta-toxin is one of the virulence factors of the strains, but the mechanism of intestinal pathogenesis is unclear. Here, we investigated the effects of delta-toxin on the mouse ileal loop. Delta-toxin caused fluid accumulation and intestinal permeability to fluorescein isothiocyanate (FITC)-dextran in the mouse ileal loop in a dose- and time-dependent manner. Treatment with delta-toxin induced significant histological damage and shortening of villi. Delta-toxin activates a disintegrin and metalloprotease (ADAM) 10, leading to the cleavage of E-cadherin, the epithelial adherens junction protein, in human intestinal epithelial Caco-2 cells. In this study, E-cadherin immunostaining in mouse intestinal epithelial cells was almost undetectable 1 h after toxin treatment. ADAM10 inhibitor (GI254023X) blocked the toxin-induced fluid accumulation and E-cadherin loss in the mouse ileal loop. Delta-toxin stimulated the shedding of intestinal epithelial cells. The shedding cells showed the accumulation of E-cadherin in intracellular vesicles and the increased expression of active caspase-3. Our findings demonstrate that delta-toxin causes intestinal epithelial cell damage through the loss of E-cadherin cleaved by ADAM10. View Full-Text
Keywords: C. perfringens delta-toxin; fluid accumulation; intestinal damage; E-cadherin C. perfringens delta-toxin; fluid accumulation; intestinal damage; E-cadherin
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MDPI and ACS Style

Seike, S.; Takehara, M.; Kobayashi, K.; Nagahama, M. Clostridium perfringens Delta-Toxin Damages the Mouse Small Intestine. Toxins 2019, 11, 232.

AMA Style

Seike S, Takehara M, Kobayashi K, Nagahama M. Clostridium perfringens Delta-Toxin Damages the Mouse Small Intestine. Toxins. 2019; 11(4):232.

Chicago/Turabian Style

Seike, Soshi, Masaya Takehara, Keiko Kobayashi, and Masahiro Nagahama. 2019. "Clostridium perfringens Delta-Toxin Damages the Mouse Small Intestine" Toxins 11, no. 4: 232.

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