The Clostridium perfringens epsilon-toxin

Payne, Dean; Williamson, E. Diane; Titball, Richard W.

doi:10.1097/00013542-199712001-00014

Cited by 19 publications

(13 citation statements)

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“…However, it is not yet clear whether hepatitis A virus cellular receptor 1 is a functional ETX receptor. Moreover, although ETX does not directly interact with a lipid, the lipid environment of the ETX receptor is critical for the binding of ETX to a cell surface, because it is prevented by detergent treatment [86,90]. It is noteworthy that ETX can interact with artificial lipid bilayers and form functional channels, without the requirement for a specific receptor, in contrast to cell membrane, albeit less efficiently than in MDCK cells.…”

Section: Molecular and Cellular Mechanism Of Actionmentioning

confidence: 99%

Epsilon toxin: a fascinating pore‐forming toxin

2011

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Epsilon toxin (ETX) is produced by strains of Clostridium perfringens classified as type B or type D. ETX belongs to the heptameric β‐pore‐forming toxins including aerolysin and Clostridium septicum alpha toxin, which are characterized by the formation of a pore through the plasma membrane of eukaryotic cells consisting in a β‐barrel of 14 amphipatic β strands. By contrast to aerolysin and C. septicum alpha toxin, ETX is a much more potent toxin and is responsible for enterotoxemia in animals, mainly sheep. ETX induces perivascular edema in various tissues and accumulates in particular in the kidneys and brain, where it causes edema and necrotic lesions. ETX is able to pass through the blood–brain barrier and stimulate the release of glutamate, which accounts for the symptoms of nervous excitation observed in animal enterotoxemia. At the cellular level, ETX causes rapid swelling followed by cell death involving necrosis. The precise mode of action of ETX remains to be determined. ETX is a powerful toxin, however, it also represents a unique tool with which to vehicle drugs into the central nervous system or target glutamatergic neurons.

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Section: Molecular and Cellular Mechanism Of Actionmentioning

confidence: 99%

Epsilon toxin: a fascinating pore‐forming toxin

2011

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“…Besides massive necrosis in the brain, pulpy kidneys are noticeable in animals that have died due to enterotoxemia (22). Epsilon-toxin exhibits cytotoxicity towards MDCK cells derived from dog renal distal tubules or collecting ducts but not towards any other cell lines (17,21,24). Moreover, epsilon-toxin was reported to be most abundant in the kidneys when intravenously (i.v.)…”

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confidence: 98%

“…Although some pycnotic and exfoliated epithelial cells were observed in distal tubuli and collecting ducts, there were no findings indicative of severe renal injury. Bilateral nephrectomy increased the mouse lethality of the toxin, suggesting that the kidney contributes to the host defense against the lethal toxicity of epsilon-toxin.Epsilon-toxin produced by Clostridium perfringens types B and D is a potent toxin that is responsible for rapidly fatal enterotoxemia in livestock (17,22). The toxin has been well defined in terms of the proteolytic activation of epsilon-protoxin (7, 10), its pore-forming ability in Madin-Darby canine kidney (MDCK) cell membranes (12, 18) and artificial lipid bilayers (19), and its heptamerization in detergent-insoluble glycosphingolipid-enriched microdomains (10, 11).…”

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confidence: 99%

“…Epsilon-toxin produced by Clostridium perfringens types B and D is a potent toxin that is responsible for rapidly fatal enterotoxemia in livestock (17,22). The toxin has been well defined in terms of the proteolytic activation of epsilon-protoxin (7,10), its pore-forming ability in Madin-Darby canine kidney (MDCK) cell membranes (12,18) and artificial lipid bilayers (19), and its heptamerization in detergent-insoluble glycosphingolipid-enriched microdomains (10,11).…”

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Accumulation of Clostridium perfringens Epsilon-Toxin in the Mouse Kidney and Its Possible Biological Significance

Tamai¹,

Ishida²,

Miyata³

et al. 2003

Infect Immun

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In this paper we show that Clostridium perfringens epsilon-toxin accumulates predominantly in the mouse kidney, where it is distributed mainly in glomeruli, capillaries, and collecting ducts. Although some pycnotic and exfoliated epithelial cells were observed in distal tubuli and collecting ducts, there were no findings indicative of severe renal injury. Bilateral nephrectomy increased the mouse lethality of the toxin, suggesting that the kidney contributes to the host defense against the lethal toxicity of epsilon-toxin.Epsilon-toxin produced by Clostridium perfringens types B and D is a potent toxin that is responsible for rapidly fatal enterotoxemia in livestock (17,22). The toxin has been well defined in terms of the proteolytic activation of epsilon-protoxin (7, 10), its pore-forming ability in Madin-Darby canine kidney (MDCK) cell membranes (12, 18) and artificial lipid bilayers (19), and its heptamerization in detergent-insoluble glycosphingolipid-enriched microdomains (10, 11). However, the pathogenic mechanisms involved in the lethality of epsilontoxin remain largely unknown, except that it exhibits toxicity towards neuronal cells (2,8,9) and blood vessels in the brains of mice and rats (1, 3, 4). Besides massive necrosis in the brain, pulpy kidneys are noticeable in animals that have died due to enterotoxemia (22). Epsilon-toxin exhibits cytotoxicity towards MDCK cells derived from dog renal distal tubules or collecting ducts but not towards any other cell lines (17,21,24). Moreover, epsilon-toxin was reported to be most abundant in the kidneys when intravenously (i.v.) administered to mice (13). However, nothing is known about its nephrotoxicity.The aim of this study was to determine the distribution of epsilon-toxin in the mouse kidney and also its nephrotoxicity. Male ddY mice (4 weeks old; SLC Japan, Shizuoka, Japan) were used. The epsilon-protoxin and epsilon-toxin used in this study were recombinant toxins, which were purified, activated, and labeled with [␥-35 S]ATP as described previously (11). The intravenous 50% lethal dose of epsilon-toxin was determined to be approximately 20 ng per mouse. The time to death after challenge estimated for mice susceptible to 15 ng of epsilontoxin was 8.3 Ϯ 0.4 h (mean Ϯ standard error [SE], n ϭ 5), and that for mice receiving 500 ng of epsilon-toxin was 0.35 Ϯ 0.01 h (mean Ϯ SE, n ϭ 5).First, we examined, by whole-body autoradiography (WBA), whether epsilon-toxin is accumulated predominantly in the mouse kidney in accordance with the results obtained by others using a different methodology (13). One hundred nanograms of 35 S-epsilon-toxin or 35 S-epsilon-protoxin was i.v. injected into a mouse through a tail vein. The mouse given 35 S-epsilontoxin was frozen in dry ice-acetone at approximately 1 h postinjection (p.i.) immediately after death. The mouse given 35 Sepsilon-protoxin was sacrificed by cervical dislocation at 1 h p.i., followed by freezing in dry ice-acetone. Frozen sections (50 m each) were prepared with an autocryotome (NA-500F; Nakagawa Seisaku...

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“…The terminal phase of enterotoxemia is characterized by neurological disorders (opisthotonus, convulsions, and agonal struggling). Epsilon toxin increases the permeability of the brain vasculature and causes perivascular edema, which is probably responsible for neuronal damage and neurological disorders (5,6). In addition, epsilon toxin could directly interact with hippocampus neurons leading to an excessive release of glutamate (7,8).…”

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confidence: 99%

Clostridium perfringens Epsilon Toxin Induces a Rapid Change of Cell Membrane Permeability to Ions and Forms Channels in Artificial Lipid Bilayers

Petit

Maier

Gibert

et al. 2001

Journal of Biological Chemistry

142

155

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Epsilon toxin is a potent toxin produced by Clostridium perfringens types B and D, which are responsible for a rapidly fatal enterotoxemia in animals. One of the main properties of epsilon toxin is the production of edema. We have previously found that epsilon toxin causes a rapid swelling of Madin-Darby canine kidney cells and that the toxin does not enter the cytosol and remains associated with the cell membrane by forming a large complex (Petit, L., Gibert, M., Gillet, D., LaurentWinter, C., Boquet, P., and Popoff, M. R. (1997) J. Bacteriol. 179, 6480 -6487). Here, we report that epsilon toxin induced in Madin-Darby canine kidney cells a rapid decrease of intracellular K ؉ , and an increase of Cl ؊ and Na ؉ , whereas the increase of Ca 2؉ occurred later. The entry of propidium iodide that was correlated with the loss of cell viability monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test indicates that epsilon toxin formed large pores. In artificial lipid bilayers, epsilon toxin caused current steps with a single-channel conductance of 60 pS in 100 mM KCl, which represented general diffusion pores. The channels were slightly selective for anions, but cations could also penetrate. Epsilon toxin formed wide and water-filled channels permeable to hydrophilic solutes up to a molecular mass of at least 1 kDa, which probably represents the basic mechanism of toxin action on target cells.

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The Clostridium perfringens epsilon-toxin

Cited by 19 publications

References 0 publications

Epsilon toxin: a fascinating pore‐forming toxin

Epsilon toxin: a fascinating pore‐forming toxin

Accumulation of Clostridium perfringens Epsilon-Toxin in the Mouse Kidney and Its Possible Biological Significance

Clostridium perfringens Epsilon Toxin Induces a Rapid Change of Cell Membrane Permeability to Ions and Forms Channels in Artificial Lipid Bilayers

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