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Structure and function of the nontoxic components of Clostridium botulinum progenitor toxins.

Research Project

Project/Area Number 08457088
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

OGUMA Keiji  Okayama University, Medical School, Professor, 医学部, 教授 (00002262)

Co-Investigator(Kenkyū-buntansha) INOUE Kaoru  Okayama University, Medical School, Assistant, 医学部, 助手 (40260103)
FUJINAGA Yukako  Okayama University, Medical School, Assistant., 医学部, 助手 (60252954)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥4,500,000 (Direct Cost: ¥4,500,000)
KeywordsC.botulinum / botulinum toxin / nontoxic component / Hemagglutinin / ポツリヌス菌 / ポツリヌス毒素
Research Abstract

Clostridium botulinum neurotoxins (Mr.150kDa) associate with nontoxic components in the cultures or in the foods, and become large complexes designated 12S (300 kDa), 16S (500 kDa), and 19S (900 kDa) progenitor toxins. Type A strain produces three formes of toxins, 12S,16S,and 19S,and type B,C,and D produce two formes of toxins, 12S and16S.Types E,F and G produce only one type of toxin ; types E and F produce 12S toxin, and type G produces 16 toxin. The 12S toxin consists of a neurotoxin and a nontoxic component showing no hemagglutinin (HA) activity, described here as a NTNH.The 16S and 19S toxins are formed by conjugation of 12S toxin with HA.The structure of progenitor toxins was clarified by both genetic- and protein chemical- analyzes. The conclusions drawn are 1) any types of HAs consist of four subcomponents, 53,33,22-23, and 17 kDa, which associated in the ratio of 1 : 2 : 1 : 1,2) the 22-2 kDa subcomponent consists of several proteins having a slightly different Mr, 3) type A … More 19S and 16S toxins consist of the same protein components. It was postulated that the 19S toxin is a dimmer of the 16S toxin cross-linked by HA-33,4) the NTNHs of type A,C,and D 12S toxins have a cleavage on their N-terminal regions, and are separated into two parts on SDS-PAGE.A multiple alignment of N-terminal regions of the NTNHs of types A,C,D,E,and F demonstrated that the cleavage occurs in a region including a short repeat sequence, and that types E and F which produce only 12S toxin lack this region. It was thought that the processing in NTNH is the reason why the 12S and 16S (and 19S) toxins exist in the same culture, 5) the receptors of red blood cells for HA arre different depending on the types of toxins ; A and B toxins bind to neutral lipids, whereas C and D toxins bind to sialic acids in both glicolipids (such as GM3 and sialylparagloboside) and glycoproteins (such as glycophorin), 6) In type C,HA-33 and HA-53 out of four subcomponents of HA,have the binding activity to the erythrocytes, 7) HA plays an important role for the progenitor toxin to bind to the epithelial cells of small intestine, that leads to efficient absorption of the HA-positive toxins is small intestine s compared with the HA-negative toxin. Less

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (57 results)

All Other

All Publications (57 results)

  • [Publications] Moriishi, K., et al.: "Mosaic structures of neurotoxins produced from Clostridium botulinum types C and D organisms." Biochim.Biophys Acta.1307・2. 123-126 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Inoue, K., et al.: "Molecular composition of Clostridium botulinum type A progenitor toxins." Infect.Immun.64・5. 1589-1594 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Moriishi, K., et al.: "Molecular cloning of the gene encoding the mosaic neurotoxin composed of parts of botulinum neurotoxin types C and D and PCR detection of its gene from Clostridium botulinum type C organisms." Appl.Environ.Microbiol.62・2. 662-667 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takeshi, K., et al.: "Simple method for detection of Clostridium botulinum type A to F neurotoxin genes by polymerase chain reaction." Microbiol.Immunol.40・1. 5-11 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 小熊 惠二 他: "毒素産生菌による感染症-ボツリヌス症-" 科学療法の領域. 12・4. 27-36 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 井上 薫 他: "ボツリヌス毒素のbinding assay.グリコバイオロジー実験プロトコール(糖タンパク質・糖脂質・プロテオグリカン)" 細胞工学. 別冊. 230-235 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 小熊 惠二 他: "細菌毒素と小児疾患-細菌毒素とは-" 小児内科. 28・9. 1171-1178 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 小熊 惠二 他: "感染症における病原因子-ボツリヌス菌-" 臨床検査. 41・6. 646-654 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 小熊 惠二 他: "感染症の脅威-毒素型食中毒-" 総合臨牀. 46・5. 1531-1539 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujinaga, Y., et al.: "The haemagglutinin of Clostridium botulinum type C progenitor toxin plays an essential role in binding of toxin to the epithelial cells of guinea pig small intestine,leading to the efficient absorption of the toxin." Microbiol.143. 3841-3847 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, K., et al.: "Clostridium botulinum Toxin." J.Toxicol.-Toxin Reviews. 16・4. 253-266 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 小熊 惠二 他: "ボツリヌス毒素" 治療学. 31・12. 1467-1473 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 井上 薫 他: "ボツリヌス神経毒素-無毒成分複合体の構造と機能" 蛋白質 核酸 酵素. 42・10. 2049-2060 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 小熊 惠二: "細菌の外毒素" 現代医療. 30・5 (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 小熊 惠二 他: "乳児ボツリヌス症" 臨床と微生物. 25・2. 179-187 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, K., et al.: "Molecular Approaches to Food Safety" M.Eklund,J.L.Richard,K.Mise, 532 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 小熊 惠二 他: "ウイルス・細菌感染症newファイル(実験医学別冊メディカル用語ライブラリー)" 永井美之,渡邊治雄, 243 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, K., et al.: "Microbial foodborne diseases : Mechanisms of pathogenesis and toxin synthesis." Linz J.E.,Bhatnagar D.,Stein M.A.,and Cary J.W. (in press), (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 小熊 惠二 他: "毒素産生菌とその感染症" 竹田美文,本田武司(in press), (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Moriishi, K., et al.: "Mosaic structures of neurotoxins produced from Clostridium botulinum types C and D organisms." Biochim.Biophys Acta.1307/2. 123-126 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Inoue, K., et al.: "Molecular composition of Clostridium botulinum type A progenitor toxins" Infect.Immun.64/5. 1589-1594 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Moriishi, K., et al.: "Molecular cloning of the gene encoding the mosaic neurotoxin composed of parts of botulinum neurotoxin types C1 and D and PCR detection of its gene from Clostridium botulinum type C organisms" Appl.Environ.Microbiol.62/2. 662-667 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takeshi, K., et al.: "Simple method for detection of Clostridium botulinum type A to F neurotoxin genes by polymerase chain reaction." Microbiol.Immunol.40/1. 5-11 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, K., et al.: "Botulism." Antibiotics & Chemotherapy. 12/4. 27-36 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Inoue, K., et al.: "Binding assay of botulinum progenitor toxin." Cell technology (separate volume). 230-235 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, K., et al.: "Bacterial toxins." Japanese Journal of Pediatric Medicine. 28/9. 1171-1178 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, K., et al.: "Pathogenicity of Clstridium botulinum" Journal of Medical technology. 41/6. 646-654 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, K., et al.: "Food poisning caused by S.aureus and C.botulinum." Clinic All-round. 41/6. 1531-1539 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujinaga, Y., et al.: "The haemagglutinin of Clostridium botulinum type C progenitor toxin plays an essential role in binding of toxin to the epithelial cells of guinea pig small intestine, leading to the efficient absorption of the toxin." Microbiol.143. 3841-3847 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, K., et al.: "Clostridium botulinum toxin." J.Toxicol.-Toxin Reviews. 16/4. 253-266 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, K., et al.: "Botulinum toxin" Biomedicine & Therapentics. 31/12. 1467-14731 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Inoue, K., et al.: "Structure and fanction of Clostridium botulinum progenitor toxins." Protein, Nucleic Acid and Enzyme. 42/10. 2049-2060 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, K., et al.: "Infant botulism." Clinical Microbiology. 25/2. 179-187 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, K., et al.: "Bacterial exotoxin" Gendaiiryo. 30/5 (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, Y., et al.: Molecular Approaches to Food Safety. M.Eklund, J.L,Richard, K.Mise (eds)., 532 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, K., et al.: Microbial foodborne diseases : Mechanimsm of pathogenesis and toxin synthesis. Linz J.E., Bhatnagar D., Stein M.A., and Cary J.W.(eds) (in press), 1997

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, K., et al.: The infection caused by toxin-producing bacteria.Takeda, Y., and Honda, T.(eds) (in press.), 1997

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oguma, K., et al.: New file of virus and bacterial infection. Nagai, Y., and Watanabe, H.(eds), 243 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujinaga,Y.,et al.: "The haemagglutinin of Clostridium botulinum type C progenitor toxin plays an essential role in binding of toxin to the epithelial cells of guinea pig small intestine,leading to the efficient absorption of the toxin." Microbiol.143. 3841-3847 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Oguma,K.,et al.: "Clostridium botulinum." J.Toxicol.-Toxin Reviews. 16・4. 253-266 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小熊惠二他: "ポツリヌス毒素" 治療学. 31・12. 1467-1473 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 井上薫他: "ポツリヌス神経毒素・無毒成分複合体の構造と機能" 蛋白質 核酸 酵素. 42・10. 2049-2060 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小熊惠二: "細菌の外毒素" 現代医療. 30・5(in press). (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小熊惠二: "乳児ポツリヌス症" 臨床と微生物. 25・2(in press). (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Oguma,K.,et al.: "Microbial foodborne diseases : Mechanisms of pathogenesis and toxin synthesis." Linz J.E.,Bhatnagar D.,Stein M.A.,and Cary J.W.(in press), (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小熊惠二他: "毒素産生菌とその感染症" 竹田美文, 本田武司(in press), (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小熊惠二他: "ウィルス・細菌感染newファイル(実験医学別冊メディカル用語ライブラリー)" 永井美之, 渡邊治雄, 243 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Moriishi,K.,et al.: "Mosaic atructures of neurotoxins produced from Clostridium botulinum types C and D organisms." Biochim.Biophys Acta.1307・2. 123-126 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Inoue,K.,et al.: "Molecular composition of Clostridium botulinum type A progenitor toxins." Infect.Immun.64・5. 1589-1594 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Moriishi,K.,et al.: "Molecular cloning of the gene encoding the mosaic neurotoxin composed of parts of botulinum neurotoxin types C1 and D and PCR detection of its gene from Clostridium botulinum type C organisms." Appl.Environ.Microbiol.62・2. 662-667 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takeshi,K.,et al.: "Simple method for detection of Clostridium botulinum type A to F neurotoxin genes by polymerase chain reaction." Microbiol.Immunol.40・1. 5-11 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 小熊惠二 他: "毒素産生菌による感染症-ボツリヌス症-" 科学療法の領域. 12・4. 27-36 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 井上薫 他: "ボツリヌス毒素のbinding assay.グリコバイオロジー実験プロトコール(糖タンパク質・糖脂質・プロテオグリカン)" 細胞工学. 別冊. 230-235 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 小熊惠二 他: "細菌毒素と小児疾患-細菌毒素とは-" 小児内科. 28・9. 1171-1178 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 小熊惠二 他: "感染症における病原因子-ボツリヌス菌-" 臨床検査. 41・6(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 小熊惠二 他: "感染症の脅威-毒素型食中毒-" 綜合臨牀. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Oguma,K.,et al.: "Molecular Approaches to Food Safety" M.Eklund,J.L.Richard,K.Mise, 532 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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