Identification and Characterization of a New Enterotoxin Produced by Clostridium perfringens Isolated from Food Poisoning Outbreaks

Irikura, Daisuke; Monma, Chie; Suzuki, Yasunori; Nakama, Akiko; Kai, Akemi; Fukui-Miyazaki, Aya; Horiguchi, Yasuhiko; Yoshinari, Tomoya; Sugita-Konishi, Yoshiko; Kamata, Yoichi

doi:10.1371/journal.pone.0138183

Cited by 34 publications

(36 citation statements)

References 34 publications

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“…It deserves brief mention that two studies recently linked CPE-negative type A strains to some food poisoning cases in Japan [ 11 , 12 ]. However, the responsible toxin made by those strains resembles iota toxin, so those cases might better be considered as type E human food poisoning.…”

Section: The Importance Of Cpe In Gastrointestinal (Gi) Diseasementioning

confidence: 99%

Clostridium perfringens Enterotoxin: Action, Genetics, and Translational Applications

Freedman

Shrestha

McClane

2016

Toxins

167

120

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Clostridium perfringens enterotoxin (CPE) is responsible for causing the gastrointestinal symptoms of several C. perfringens food- and nonfood-borne human gastrointestinal diseases. The enterotoxin gene (cpe) is located on either the chromosome (for most C. perfringens type A food poisoning strains) or large conjugative plasmids (for the remaining type A food poisoning and most, if not all, other CPE-producing strains). In all CPE-positive strains, the cpe gene is strongly associated with insertion sequences that may help to assist its mobilization and spread. During disease, CPE is produced when C. perfringens sporulates in the intestines, a process involving several sporulation-specific alternative sigma factors. The action of CPE starts with its binding to claudin receptors to form a small complex; those small complexes then oligomerize to create a hexameric prepore on the membrane surface. Beta hairpin loops from the CPE molecules in the prepore assemble into a beta barrel that inserts into the membrane to form an active pore that enhances calcium influx, causing cell death. This cell death results in intestinal damage that causes fluid and electrolyte loss. CPE is now being explored for translational applications including cancer therapy/diagnosis, drug delivery, and vaccination.

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Section: The Importance Of Cpe In Gastrointestinal (Gi) Diseasementioning

confidence: 99%

Clostridium perfringens Enterotoxin: Action, Genetics, and Translational Applications

Freedman

Shrestha

McClane

2016

Toxins

167

120

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“…In-vitro studies show that ITX can induce permeability changes in Caco-2 cells monolayers [15]. In-vivo studies with other clostridial binary toxins, like CDT from C. difficile [31,32] and BEC from C. perfringens [33,34], also described fluid accumulation in the intestinal lumen. In the present report, fluid imbalance was determined by two different approaches, enteropooling and intestinal loops.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Effects of Clostridium perfringens iota toxin in the small intestine of mice

Redondo

Dailoff

et al. 2017

Anaerobe

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Iota toxin is a binary toxin solely produced by Clostridium perfringens type E strains, and is structurally related to CDT from C. difficile and CST from C. spiroforme. As type E causes hemorrhagic enteritis in cattle, it is usually assumed that associated diseases are mediated by iota toxin, although evidence in this regard has not been provided. In the present report, iota toxin intestinal effects were evaluated in vivo using a mouse model. Histological damage was observed in ileal loops treated with purified iota toxin after 4 h of incubation. Luminal iota toxin induced fluid accumulation in the small intestine in a dose dependent manner, as determined by the enteropooling and the intestinal loop assays. None of these changes were observed in the large intestine. These results suggest that C. perfringens iota toxin alters intestinal permeability, predominantly by inducing necrosis and degenerative changes in the mucosal epithelium of the small intestine, as well as changes in intestinal motility. The obtained results suggest a central role for iota toxin in the pathogenesis of C. perfringens type E hemorrhagic enteritis, and contribute to remark the importance of clostridial binary toxins in digestive diseases.

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“…At present, more than 20 C. perfringens toxins have been identified, and there may be additional toxins that have yet to be identified (Hatheway, 1990;Petit et al, 1999;Amimoto et al, 2007;Keyburn et al, 2008;Yonogi et al, 2014;Irikura et al, 2015;Mehdizadeh Gohari et al, 2016). Based on the primary toxins produced by C. perfringens and differences in pathogenesis among strains, C. perfringens strains are divided into seven types according to a recent revision (Type A-G, Table 1; Rood et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Sialidases From Clostridium perfringens and Their Inhibitors

Wang

2020

Front. Cell. Infect. Microbiol.

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Clostridium perfringens is an important human and animal pathogen that is the primary causative agent of necrotizing enteritis and enterotoxemia in many types of animals; it causes traumatic gas gangrene in humans and animals and is associated with cases of food poisoning in humans. C. perfringens produces a variety of toxins as well as many enzymes, including three sialidases, NanH, NanI, and NanJ. Sialidases could be important virulence factors that promote the pathogenesis of C. perfringens. Among them, NanI promotes the colonization of C. perfringens in the intestinal tract and enhances the cytotoxic activity and association of several major C. perfringens toxins with host cells. In recent years, studies on the structure and functions of sialidases have yielded interesting results, and the functions of sialic acid and sialidases in bacterial pathogenesis have become a hot research topic. An in-depth understanding and additional studies of sialidases will further elucidate mechanisms of C. perfringens pathogenesis and could promote the development and clinical applications of sialidase inhibitors. This article reviews the structural characteristics, expression regulation, roles of sialidases in C. perfringens pathogenesis, and effects of their inhibitors.

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Identification and Characterization of a New Enterotoxin Produced by Clostridium perfringens Isolated from Food Poisoning Outbreaks

Cited by 34 publications

References 34 publications

Clostridium perfringens Enterotoxin: Action, Genetics, and Translational Applications

Clostridium perfringens Enterotoxin: Action, Genetics, and Translational Applications

Effects of Clostridium perfringens iota toxin in the small intestine of mice

Sialidases From Clostridium perfringens and Their Inhibitors

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