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Analysis of the activation and mode of action of Clostridium perfringens ε-toxin

Research Project

Project/Area Number 09670286
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionKagawa Medical University

Principal Investigator

MATSUSHITA Osamu (1999)  Kagawa Medical University, Microbiology, assistant professor, 医学部, 助教授 (00209537)

南 純三朗 (1997-1998)  香川医科大学, 医学部, 助教授 (40157566)

Co-Investigator(Kenkyū-buntansha) KATAYAMA Seiichi  Kagawa Medical University, Microbiology, research associate, 医学部, 助手 (70169473)
OKABE Akinobu  Kagawa Medical University, Microbiology, professor, 医学部, 教授 (20093677)
松下 治  香川医科大学, 医学部, 助手 (00209537)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥100,000 (Direct Cost: ¥100,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsClostridium perfringens / epsilon-toxin / lambda-toxin / mouse lethality / hippocampus / trypsin / トリプシン / ε毒素 / 組換え毒素
Research Abstract

1. The activation of Clostridium perfringens epsilon-prototoxin (ε-prototoxin) by λ-toxin, trypsin and chymotrypsin was examined. The mouse lethality test showed that the 50% lethal doses (LDィイD250ィエD2) of the prototoxin with and without λ-toxin treatment were 110 and 70,000 ng/kg of body weight, respectively. LDィイD250ィエD2 of the prototoxin treated with trypsin and trypsin plus chymotrypsin were 320 and 65 ng/kg of body weight, respectively. Determination of the N-terminal amino acid sequence of each activated 8-prototoxin revealed that λ-toxin cleaved between the 10th and 11th amino acid residues from the N-terminus of the prototoxin, while trypsin and trypsin plus chymotrypsin did so between the 13th and 14th amino acid residues. The C-terminus deduced from the molecular weight is located at the 23th or 30th amino acid residue from the C-terminus of the prototoxin, suggesting that removal of not only N- but also C-terminal peptides is responsible for the activation of the prototoxin.
2. The neurotoxicity of ε-toxin was examined by histological examination of the rat brain. Injection of ε-toxin at a sublethal dose, 50 ng/kg, caused neuronal damage predominantly in the hippocampus: pyramidal cells in the hippocampus showed marked shrinkage and karyopyknosis, and the cells lost the immunoreactivity to microtubule-associated protein 2 (MAP-2). Timm's zinc staining revealed that zinc ions were depleted in the mossy layers of the CA3 subfield containing glutamate as a synaptic transmitter. Prior injection of either a glutamate-release inhibitor or glutamate-receptor antagonist protected the hippocampus from the neuronal damage caused by 8-toxin. These results suggest that 8-toxin acts on the glutamatergic system and evokes excessive release of glutamate, leading to neuronal damage.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Minami,J.: "Kambda-toxin of Clostridium perfringens activates the precursor of epsilon-toxin by releasing its N-and C-terminal peptides"Moicrobiol.immunol.. 41. 527-535 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyamoto,O.: "Neurotoxicity of Clostridium perfringens epsilon-toxin for the rat hippocampus via the glutamatergic system"InfTect.Immun.. 66. 2501-2508 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Junzaburo Minami: "Lambda-toxin of Clostridium perfringens activates the precursor of epsilon-toxin by releasing its N- and C-terminal peptides"Microbiology and Immunology. 41(7). 527-535 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Osamu Miyamoto: "Neurotoxicity of Clostridium perfringens epsilon-toxin for the rat hippocampus via the glutamatergic system"Infection and Immunity. 66(6). 2501-2508 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Osamu Miyamoto: "Neurotoxicity of Clostridium perfringens epsilon-toxin for the rat hippocampus via the glutamatergic system" Infection and Immunity. 66・6. 2501-2508 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Junzaburo Minami: "Lambda-toxin of Clostridium perfringens activates the precursor of epsilon-toxin by releasing its N-and C-terminal peptides" Microbiology and Immunology. 41・7. 527-535 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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