Histidine residues in Clostridium perfringens epsilon toxin

Sakùrai, Jun; Nagahama, Masahiro

doi:10.1111/j.1574-6968.1987.tb02219.x

Cited by 25 publications

(6 citation statements)

References 13 publications

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“…The epsilon toxin has been purified from some type D strains, and shown experimentally to increase vascular permeability in the brain [2], cause kidney damage [3] and contraction of the ileum [4], and to possess cardiovascular and pressor activities [5]. Little is known about the mode of action of epsilon toxin, and no enzymatic activity has yet been assigned to it, but the importance of certain amino acid residues for toxicity has been demonstrated [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Comparison of the nucleotide sequence and development of a PCR test for the epsilon toxin gene of Clostridium perfringens type B and type D

Harvard

1992

FEMS Microbiology Letters

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The sequence of the epsilon toxin gene of Clostridium perfringens type D was determined and compared with that of the previously reported type B sequence. It showed two nucleotide changes in the open reading frame, giving rise to one amino acid substitution. The promoter sequences were not homologous, and different putative -35 and -10 regions have been identified in each. The sequence information was used to develop PCR primers which were specific for the epsilon toxin gene. The utility of this system for identifying type B or D strains of C. perfringens was demonstrated.

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Section: Introductionmentioning

confidence: 99%

Comparison of the nucleotide sequence and development of a PCR test for the epsilon toxin gene of Clostridium perfringens type B and type D

Harvard

1992

FEMS Microbiology Letters

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“…Moreover, it was shown that labeled toxin specifically accumulates in the brains of mice after intravenous injection and that the lethal activity of the toxin depends on its specific binding in the brain, probably to a sialoglycoprotein (28,29). Certain amino acids of epsilon-toxin, such as histidine, tryptophan, and aspartic or glutamic acid have been found to be essential for its biological activity (35)(36)(37)(38).…”

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confidence: 99%

Clostridium perfringens epsilon-toxin acts on MDCK cells by forming a large membrane complex

et al. 1997

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Epsilon-toxin is produced by. Here we present evidence that epsilon-toxin cytotoxic activity is correlated with the formation of a large membrane complex (about 155 kDa) and efflux of intracellular K ؉ without entry of the toxin into the cytosol. Epsilon-toxin induced swelling, blebbing, and lysis of MDCK cells. Iodolabeled epsilon-toxin bound specifically to MDCK cell membranes at 4 and 37°C and was associated with a large complex (about 155 kDa). The binding of epsilon-toxin to the cell surface was corroborated by immunofluorescence staining. The complex formed at 37°C was more stable than that formed at 4°C, since it was not dissociated by 5% sodium dodecyl sulfate and boiling.Epsilon-toxin is produced by Clostridium perfringens types B and D and is responsible for a rapidly fatal enterotoxemia in sheep and other animals which causes heavy economic losses (24). It is synthesized as a relatively inactive prototoxin (296 amino acids) which is converted to a highly active mature protein by proteolytic removal of a basic N-terminal peptide (13 amino acids) (3, 16).Epsilon-toxin is lethal and dermonecrotic. It has been reported to increase intestinal permeability (4), to cause kidney damage (9), to elevate blood pressure (27, 39), and to cause contraction of isolated rat ileum (40). A basic property of epsilon-toxin is that it increases vascular permeability. The toxin binds to vascular endothelial cells and causes severe vascular damage and edema in various organs (brain, heart, lung, and kidney) (5, 9). It was reported that the major pathological changes caused by enterotoxemia appear to occur in the brain (12). Moreover, it was shown that labeled toxin specifically accumulates in the brains of mice after intravenous injection and that the lethal activity of the toxin depends on its specific binding in the brain, probably to a sialoglycoprotein (28,29). Certain amino acids of epsilon-toxin, such as histidine, tryptophan, and aspartic or glutamic acid have been found to be essential for its biological activity (35)(36)(37)(38).Recently, it has been found that epsilon-toxin has 20 and 27% identity with Mtx2 and Mtx3 toxins, respectively, of Bacillus sphaericus (22, 43) and 26.5% identity with the open reading frame c53 of Bacillus thuringiensis. However, the mechanism of action of these mosquitocidal toxins is unknown.The Madin-Darby canine kidney (MDCK) cell line was found to be susceptible to epsilon-toxin. The alteration of cell viability determined by the conversion of 5-(3-carboxymethoxyphenyl)-2-(4,5-dimethylthiazolyl)-3-(4-sulfophenyl) tetrazolium to a water-soluble formazan by the mitochondrial cytochrome systems or by the neutral red assay (an indicator of lysosomal integrity) was correlated with the lethal activity of epsilon-toxin in mice (21, 30). The cytotoxic effects were found to be very rapid (2.5 min) and potentiated by EDTA (21). The morphological effects of epsilon-toxin on cells included a condensation of the nucleus and a progressive swelling of the cells (13). The permeability of polarized MD...

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“…Epsilon toxin was purified from epsilon prototoxin isolated from culture supernatants of C. perfringens type D (NCTC 8346), as described previously (12).…”

Section: Methodsmentioning

confidence: 99%

“…We have reported that the toxin binding to mouse brain is essential to the lethal activity of the toxin (5) and that the toxin shows high affinity to brain and synaptosomal membranes (6), showing that the toxin is specifically bound to brain. We also have reported that one tryptophan (9,10), one tyrosine (11) and one histidine (12) residues in the toxin are important for the toxin binding to the brain (6). Recently, it was found that the toxin specifically stimulates dopamine release in rat brain (7), suggesting that the toxin activates dopamine nerve system in brain.…”

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confidence: 99%

Effect of Clostridium perfringens Epsilon Toxin on Rat Isolated Aorta

Nagahama

Iida

Sakùrai

1993

Microbiology and Immunology

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The effect of Clostridium perfringens epsilon toxin on rat isolated aorta was investigated. The toxin caused contraction of the isolated aorta in a dose-dependent manner. The toxin induced no contraction of the isolated aorta in low-Na medium and of the tissue stored at 4 C for 7 days. However, tetrodotoxin (TTX) had no effect on the toxin-induced contraction. The toxininduced contraction was significantly inhibited by phentolamine and prazosine, but did not by atropine, mecamylamine, chlorpheniramine and methysergide. These data suggest that the toxincaused contraction is mediated through nervous system in rat isolated aorta.

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Histidine residues in Clostridium perfringens epsilon toxin

Cited by 25 publications

References 13 publications

Comparison of the nucleotide sequence and development of a PCR test for the epsilon toxin gene of Clostridium perfringens type B and type D

Comparison of the nucleotide sequence and development of a PCR test for the epsilon toxin gene of Clostridium perfringens type B and type D

Clostridium perfringens epsilon-toxin acts on MDCK cells by forming a large membrane complex

Effect of Clostridium perfringens Epsilon Toxin on Rat Isolated Aorta

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