<i>Clostridium perfringens</i>epsilon toxin causes excessive release of glutamate in the mouse hippocampus

Miyamoto, Osamu; Sumitani, Kazunori; Nakamura, Takehiro; Yamagami, Shin-ichi; Miyata, Seiko; Itano, Toshifumi; Negi, Tetsuro; Okabe, Akinobu

doi:10.1111/j.1574-6968.2000.tb09215.x

Cited by 71 publications

(22 citation statements)

References 18 publications

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“…Thus, this study also determined the toxicity of trypsin activated wild type Etx after intraperitoneal administration in groups of six mice. In previous studies trypsin activated Etx has been shown to have a LD 50 dose ranging from 70 ng/kg [20] to 320 ng/kg [10] when administered by the intravenous route to mice. There is less data on the LD 50 dose of wild type Etx when given by the intraperitoneal route to mice.…”

Section: Discussionmentioning

confidence: 96%

Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia

Bokori-Brown

Hall

Vance

et al. 2014

Vaccine

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Section: Discussionmentioning

confidence: 96%

Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia

Bokori-Brown

Hall

Vance

et al. 2014

Vaccine

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“…ETX toxin binds with high affinity to rat brain synaptosomes [111], and limited evidence suggests that the receptor might be a sialoglycoprotein [109, 111, 112]. The neurological disorders observed in several animal species seem to result from ETX action on hippocampus, leading to an excessive release of glutamate [108, 113, 114]. …”

Section: Epsilon Toxin (Etx)mentioning

confidence: 99%

Clostridium Perfringens Toxins Involved in Mammalian Veterinary Diseases

Uzal¹

2013

TOTNJ

141

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Clostridium perfringens is a gram-positive anaerobic rod that is classified into 5 toxinotypes (A, B, C, D, and E) according to the production of 4 major toxins, namely alpha (CPA), beta (CPB), epsilon (ETX) and iota (ITX). However, this microorganism can produce up to 16 toxins in various combinations, including lethal toxins such as perfringolysin O (PFO), enterotoxin (CPE), and beta2 toxin (CPB2). Most diseases caused by this microorganism are mediated by one or more of these toxins. The role of CPA in intestinal disease of mammals is controversial and poorly documented, but there is no doubt that this toxin is essential in the production of gas gangrene of humans and several animal species. CPB produced by C. perfringens types B and C is responsible for necrotizing enteritis and enterotoxemia mainly in neonatal individuals of several animal species. ETX produced by C. perfringens type D is responsible for clinical signs and lesions of enterotoxemia, a predominantly neurological disease of sheep and goats. The role of ITX in disease of animals is poorly understood, although it is usually assumed that the pathogenesis of intestinal diseases produced by C. perfringens type E is mediated by this toxin. CPB2, a necrotizing and lethal toxin that can be produced by all types of C. perfringens, has been blamed for disease in many animal species, but little information is currently available to sustain or rule out this claim. CPE is an important virulence factor for C. perfringens type A gastrointestinal disease in humans and dogs; however, the data implicating CPE in other animal diseases remains ambiguous. PFO does not seem to play a direct role as the main virulence factor for animal diseases, but it may have a synergistic role with CPA-mediated gangrene and ETX-mediated enterotoxemia. The recent improvement of animal models for C. perfringens infection and the use of toxin gene knock-out mutants have demonstrated the specific pathogenic role of several toxins of C. perfringens in animal disease. These research tools are helping us to establish the role ofThis is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

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“…It is produced by types B and D strains of the anaerobic bacterium Clostridium perfringens and primarily affects livestock in the form of rapidly fatal enterotoxemias, resulting in heavy economic losses [1]. The lethal effect of Etx has been associated with general edema and neurological alterations, leading to a glutamate-mediated excitotoxic effect and neuronal death [2], [3], [4], [5]. In addition, Etx also affects the renal system, producing congestion, interstitial hemorrhage and cytotoxicity of epithelial distal tubule cells [6], [7], [8].…”

Section: Introductionmentioning

confidence: 99%

Correlation between In Vitro Cytotoxicity and In Vivo Lethal Activity in Mice of Epsilon Toxin Mutants from Clostridium perfringens

et al. 2014

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Epsilon toxin (Etx) from Clostridium perfringens is a pore-forming protein with a lethal effect on livestock, producing severe enterotoxemia characterized by general edema and neurological alterations. Site-specific mutations of the toxin are valuable tools to study the cellular and molecular mechanism of the toxin activity. In particular, mutants with paired cysteine substitutions that affect the membrane insertion domain behaved as dominant-negative inhibitors of toxin activity in MDCK cells. We produced similar mutants, together with a well-known non-toxic mutant (Etx-H106P), as green fluorescent protein (GFP) fusion proteins to perform in vivo studies in an acutely intoxicated mouse model. The mutant (GFP-Etx-I51C/A114C) had a lethal effect with generalized edema, and accumulated in the brain parenchyma due to its ability to cross the blood-brain barrier (BBB). In the renal system, this mutant had a cytotoxic effect on distal tubule epithelial cells. The other mutants studied (GFP-Etx-V56C/F118C and GFP-Etx-H106P) did not have a lethal effect or cross the BBB, and failed to induce a cytotoxic effect on renal epithelial cells. These data suggest a direct correlation between the lethal effect of the toxin, with its cytotoxic effect on the kidney distal tubule cells, and the ability to cross the BBB.

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Clostridium perfringensepsilon toxin causes excessive release of glutamate in the mouse hippocampus

Cited by 71 publications

References 18 publications

Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia

Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia

Clostridium Perfringens Toxins Involved in Mammalian Veterinary Diseases

Correlation between In Vitro Cytotoxicity and In Vivo Lethal Activity in Mice of Epsilon Toxin Mutants from Clostridium perfringens

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