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study on diarrbeagenic toxins produced by enteric bacteria

Research Project

Project/Area Number 06454205
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Bacteriology (including Mycology)
Research InstitutionResearch Institute, International Medical Center of Japan

Principal Investigator

TAKEDA Yoshifumi  国立国際医療センター, 研究所, 所長 (30029772)

Co-Investigator(Kenkyū-buntansha) 山崎 伸二  国立国際医療センター, 研究所, 室長 (70221653)
KURAZONO Hisao  International Medical Center of Japan, Research Institute, Division Chief, 研究所, 室長 (90186487)
NISHIBUCHI Mitsuaki  Kyoto University, Faculty of Medicine, Department of Microbiology, Assoxiate Professor, 医学部, 助教授 (50189304)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1995: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1994: ¥4,600,000 (Direct Cost: ¥4,600,000)
KeywordsDiarrheagenic toxin / Escherichia coli / Shigella Dysenteriae / Vibrio cholerae / Enterohemorrhagic E.coli / Vero toxin / コレラ毒素 / ZOT
Research Abstract

(1)新しい下痢原因毒素であるcytolethal distending toxin(CDT)の遺伝子が、大腸菌以外に赤痢菌のうちS. dysenteriaeとS. sonneiにも存在することを明らかにした。しかしコレラ菌をはじめ、種々のVibrio属菌には存在しなかった。
(2)S. dysenteriaeのCDT遺伝子の構造を調べた結果、大腸菌のCDT遺伝子と11塩基が異なることを明らかにした。アミノ酸の相違は2残基であった。
(3)S. dysenteriaeのCDT遺伝子とE. coliにクローニングし、その産物を部分精製し、性状を調べた。しかし、その下痢活性を明らかにすることはできなかった。
(4)患者、環境材料などの種々の起源から分離したVibrio choleraeO1、O139およびそれ以外の血清型菌に、コレラ毒素、ZOT、ACEおよびエルトールヘモリジンの遺伝子が、どのように分布しているかを、合計1,154について調べ、それぞれの毒素遺伝子が、種々の組み合わせで存在することを明らかにした。コレラ菌による下痢に、今後これらの遺伝子産物がどのように関与しているかを調べることにより、コレラ菌の下痢原性についての詳細な情報を得る手がかりが得られた。
(5)腸管出血性大腸菌が産生するVero毒素のうち、従来variantの存在が報告さてれてないVT1について、2種類のvariantの存在を明らかにし、それぞれの構造遺伝子の塩基配列を決定した。variantの1つVT1v1については、精製を行い、精製毒素の性状を明らかにした。その結果、VT1v1はVT1より生物活性が1/40〜1/100と低いことがわかった。VT1v1とVT1とはアミノ酸配列で83%の相同性であるが、活性の低下が相同性の無いアミノ酸に起因する可能性を推定することができた。

Report

(3 results)
  • 1995 Annual Research Report
  • 1994 Annual Research Report   Final Research Report Summary
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Jun Okuda: "Distribution of the cytolethal distending toxin A gene(cdtA)among species of Shigella and Vibrio, and cloning and sequencing of the cdt gene from Shigella dysenteriae" Microbial Pathogenesis. 18. 167-172 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hisao Kurazono: "Distribution of genes encoding cholera toxin, zonula occludens toxin, accessory cholera toxin, and El Tor hemolysin in Vibrio cholerae of diverse origins" Microbial Pathogenesis. 18. 231-235 (995)

    • Related Report
      1995 Annual Research Report
  • [Publications] S.Yamasaki, G.B.nair, S.K.Bhattacharya, S.Yamamoto, H.Kurazono snd Y.Takeda: "Cryptic appearance of a new clone of vibrio cholerae serogroup O1 biotype El Tor in Calucutta, India"Microbiol. Immunol.. 41. 1-6 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.Okuda, M.Fukumoto, Y.Takeda and M.nishibuchi: "Examination of diarrheagenicity of cytolethal Toxin : Suckling mouse response to the products of the cdtABC genes of Shigella dysenteriae"Infect. Immun.. 65. 428-433 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Yamamoto, H.Kiyono, M.Yamamoto, K.Imaoka, M.Yamamoto, K.Fujihashi, F.W.van Ginkel, M.Noda, Y.Takeda and J.R..mcGhee: "A nontoxic mutant of cholera toxin elicits Th2type responses for enhanced mucosal immunity"Proc.Natl.Acad.Sci.USA. 94. 5267-5272 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Yamamoto, Y.Takeda, M.Yamamoto, H.Kurazono, K.Imaoka, M.Yamamoto, K.Fujihashi, M.Noda, H.Kiyono and J.R..mcGhee: "Mutants in the ADP-ribosyltransferase cleft of cholera toxin lack diarrheagenicity but retain adjuvanticity"J.Exp.Med.. 185. 1203-1210 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] R..Mitra, A.Basu, D.Dutta, G.B.Nair, Y.Takeda: "Resurgence of Vibrio cholerae O139 Bengal with altered antibiogram in Calcutta, India"Lancet. 348. 1181 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] A.K.Mukhopadhyay, S.Garg, R.Mita, A.Basu. K.Rajendran, D.Dutta, S.K.Bhattacharya, T.Shimada, T.Takeda, Y.Takeda, G.B.Nair: "Temporal shifts in train of vibrio cholerae strains isolated from hospitalized patients in Calcutta : a3-year(1993to1995) analysis"J.Clin.Microbiol. 34. 2537-2543 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Yamasaki, G.B.nair, S.K.Bhattacharya, S.Yamamoto, H.Kurazono and Y.Takeda: "Cryptic appearance of a new clone of vibrio cholerae serogroup O1 biotype E1 Tor in Calcutta, India"Microbiol Immunol.. 41. 1-6 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.Okuda, M.Fukumoto,Y.Takeda and M.nishibuchi: "Examination of diarrheagenicity of cytolethal Toxin : Suckling mouse response to the products of the cdtABCgenes of Shigella dysenteriae"Infect Immun.. 65. 428-433 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Yamamoto, H.Kiyono, M.Yamamoto, K.Imaoka, M.Yamamoto, K.Fujihashi, F.W.van Ginkel, M.Noda. Y.Takeda and J.R,McGhee: "A nontoxic mutant of cholera toxin elicits Th2-type responses for enhanced mucosal immumty"Proc. Natl. Acad. Sci. USA. 94. 5267-5272 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Yamamoto, Y.Takeda, M.Yamamoto, H.kurazono, K.Imaoka, M.Yamamoto, K.Fujihashi, M.Noda, H.Kiyono and J.R,McGhee: "Mutants in the ADP-ribosyltransferase cleft of cholera toxin lack diarrheagenicity but retain adjuvanticity"J.Exp.Med.. 185. 1203-1210 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] R.Mitra,A.Basu,D.Dutta,G.B.Nair, Y.Takeda: "Resurgence of Vibrio cholerae O139 Bengal with altered antibiogram in Calcutta,India"Lancet.. 348. 1181 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] A.K.Mukhopadhyay, S.Garg, R.Mita, A.Basu, K.Rajendran, D.Dutta, S.K.Bhatt,acharya, T.Shimada T.Takeda Y.Takeda G.B.Nair: "Temporal shifts in traits of vibrio choleras strains isolated from hospitalized patients in Calcutta : a3-year(1993to1995) analysis"J. Clin.Microbiol.. 34. 2537-2543 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Takeda: "A simple method of purification of Escherichia cole beatlabile enterotoxin and chslere to xin using an immobiliged..." Microbial Pathogenesis. 16. 71-76 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Takeda: "Specific detection of a Verotoxin 2 mutant,VT2vp1,by a bead-anzyme-linked immunosorbent assay" Microbiol.Immunol.38. 435-440 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Takeda: "Construction of mutant genes for a non-toyic Verotoxin 2 varsant (VT2vp1) of Eschenichia coli and.." Microbiol.Immunol.38. 441-447 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Takeda: "Distribution of genes encoding chclera toxin,zonula occludens toxin,accessory chslera toxin,and.." Microbial Pathoyenesis. 18(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Takeda: "Distribution of the cytolethal distending toxin A gene (catA) awong species of serigella and vibrio..." Microbial Pathogenesis. 18(in press). (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2017-05-19  

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