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Study on pathogenic role of hemolysins produced by Vibrio spp.

Research Project

Project/Area Number 04454196
Research Category

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

Allocation TypeSingle-year Grants
Research Field 細菌学
Research InstitutionOsaka University

Principal Investigator

HONDA Takeshi  Research Institute for Microbial Diseases, Osaka University, Department of Bacterial Infections, Professor, 微生物病研究所, 教授 (60029808)

Co-Investigator(Kenkyū-buntansha) YOH Myonsun  Research Institute for Microbial Diseases, Osaka University, Department of Bacte, 微生物病研究所, 助手 (70093482)
YAMAMOTO Koichiro  Research Institute for Microbial Diseases, Osaka University, Department of Bacte, 微生物病研究所, 助教授 (30158274)
有田 美知子  大阪大学, 微生物病研究所, 助手 (10127178)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1993: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1992: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsVibrio parahahemotyticus / Vibrio cholerae / Thermostable direct hemolysin / El tor hemolysin / Phosphorylation / Pore-formation / エルトール型溶血毒 / 変異毒素 / 前駆体 / 結合 / Pore-forming toxin / 溶血毒
Research Abstract

We found that hemolysins produced by Vibrio spp.can be classified into two major groups : (1) Thermostable direct hemolysin (TDH) of Vibrio parahaemolyticus and its related hemolysin (TRH) and (2) El tor hemolysin of V.cholerae Ol. We studied on these two representative hemolysins and obtained following results.
1.TDH and TRH
(1) We discovered a new hemolysin in culture supernatant of V.parahaemolyticus and named TRH,and we also found that TRH-gene possessig bacteria always expressed urease.
(2) It was demonstrated that TDH and TRH were simultaneously produced in certain strains of V.parahaemolyticus.
TDH/TRH recognized a receptor which is present on membrane of not only sensitive but also resistant cell and then caused a phosphorylation of a 25kDa membrane protein through activation of protein kinase C,resulted in pore-formation which has 1-2nm inner diameter.
An isogenic mutant which lost TRH gene was developed and the result of the challenge with the mutant revealed that the isogenic mutant partially lose its enteropathogenicity, suggesting the possibility that TRH actually play a role in pathogenesis of V.parahaemolyticus and that factor (s) other than TRH may also involved in the pathogenicity.
2. El Tor hemolysin
(1) El Tor hemolysin is produced as a Pre-protoxin (80kDa) and passed through inner membrane with a signal peptide. In periplasmic space, the molecule becomes protoxin (79kDa) after cleavage the signal peptide. The Pro-region of the hemoysin acts as a chaperon and facilitates excretion of the protoxin through ontermembrane. The protoxin was finally modified to be an active form, mature hemolysin, by releasing Pro-region from protoxin-form. This event occurred by hemagglutinin/protease produced by Vibrio cholerae.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (50 results)

All Other

All Publications (50 results)

  • [Publications] Xu,M.et al: "Demonstration and characterization of simultaneous production of a TDH and a TRH by clinical isolate of V.parahaemolvticus" Infection and Immunity. 62. 166-171 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tang,G.Q.et al.: "A mutant toxin of V.parahaemlyticus thermostable direct hemolysin which has lost hemolytic activity but retains ability to bind" Infection and Immunity. 62. 3299-3304 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Xu,M.et al.: "Construction and characterization of an isogenic mutant of V.parahaemolyticus having a deletion inthe TRH gene." Journal of Bacteriology. 176. 4754-4760 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Taniguchi,T.et al.: "Evidence that the N-terminal amino acid sequence of pilus colonization factor antigen III produced by human ETEC is similar to" Journal of Infectious Diseases. 170. 1049-1050 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ichinise,Y.et al.: "The effect on enterotoxicity of protease purified from Vibrio cholerae 01." FEMS Microbiol Letters. 115. 265-272 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miyagi,K.et al.: "Successful application of enzyme-1 beled oligonucleotide probe for rapid and accurate cholera-diagnosis in a clinical diagnosis" Microbiology and Immunology. 38. 301-304 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagayama,K.et al.: "Correlation between cell-associated mannose-sensitive hemagglutination by V.parahaemolyticus and adherence to a human colonic" FEMS Microbiology Letters. 120. 207-210 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimaoka,M.et al.: "Development of enzyme-labeled oligonucleotide probe for mecA gene in MRSA." Journal of Clincal Microbiology. 32. 1866-1869 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Iijima,Y.et al.: "Simultaneous outbreak due to Vibrio cholerae and Shigella dysenteriae in Kenya." Lancet. 345. 69-70 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoh,M.et al.: "Evaluation of two assay kits for TDH as an indicator of TRH produced by V.parahaemolyticus." Microbiology and Immunology. 39. 157-159 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Honda,T.et al.: "A novel method to chemically immobilize antibody on nylon and its application to the rapid and diferential detection of two toxins" Clinical and Diagnostic Laboratory Immunology. 2(in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 本田武司: "病気と細菌毒素" 化学同人, 159 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Xu, M.et al: "Demonstration and characterization of simultaneous production of a thermostable direct hemolysin (TDH) and a TDH-related hemolysin by a clinically isolated Vibrio parahaemolyticus strain, TH3766." Infect. Immun. 62. 166-171 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tang, G.Q.et al: "A mutant toxin of Vibrio parahaemolyticus thermostable direct hemolysin which has lost hemolytic activity but retains ability to bind to erythrocytes." Infect. Immun. 62. 3299-3304 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Xu, M.et al: "Construction and characterization of an isogenic mutant of Vibrio parahaemolyticus having a deletion in the thermostable direct hemolysin-related hemolysin gene (trh)." J.Bacteriol. 176. 4757-4760 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Taniguchi, T., et al: "Evidence that the N-terminal amino acid sequence of pilus colonization factor anti gen III produced by human enterotoxigenic Escherichia coli is similar to that of TcpA pilin of Vibrio cholerae." J.Infect. Dis. 170. 1049-1050 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ichinose, Y., et al: "The effect on enterotoxicity of protease purified from Vibrio cholerae Ol." FEMS Microbiol. Lett. 115. 265-272 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miyagi, K., et al: "Successful application of enzymelabeled oligonucleotide probe for rapid and accurate cholera diagnosis in a clinical laboratory." Microbio. Immu nol. 38 (4). 301-304 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagayama, K., et al: "Correlation between cell-asso-ciated mannose-sensitive hemagglutination by Vibrio parahaemolyticus and adherence to a human colonic cell line Caco-2." FEMS Microbiol. Lett. 120. 207-210 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimaoka, M., et al: "Development of enzyme-labeled oligonucleotide probe for mecA gene in methicillin-resistant Staphylococcus aureus." J.Clin. Microbiol. 32. 1866-1869 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Iijima, Y., et al: "Simultaneous outbreak due to Vibro. cholerae and Shigella dysenteriae in Kenya." Lancet. 345. 69-70 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoh, M., et al: "Evaluation of two assay kits for TDH as an indicator of TRH produced by V.Parahaemolytiucs." Microbiol. Immun. 39. 157-159 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Honda, T., et al: "A novel method to chemically immobilize antibody on nylon and its application to the rapid and differential detection of two toxins." Clin. Diagno. Lab.Immun. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Xu,M.et al.: "Demonstration and characterization of simultaneous production of a TDH and a TRH by a clinical isolate of V.parahaemolyticus" Infection and Immunity. 62. 166-171 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tang,G.Q.et al.: "A mutant toxin of V.parahaemlyticus thermostable direct hemolysin which has lost hemolytic activity but retains ability to bind" Infection and Immunity. 62. 3299-3304 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Xu,M.et al.: "Construction and characterization of an isogenic mutant of V.parahaemolyticus having a deletion inthe TRH gene" Journal of Bacteriology. 176. 4754-4760 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Taniguchi,T.et al.: "Evidence that the N-terminal amino acid sequence of pilus colonization factor antigen III produced by human ETEC is similar to" Journal of Infectious Diseases. 170. 1049-1050 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ichinise,Y. et al.: "The effect on enterotoxicityof protease purified from Vibrio cholerae 01." FEMS Microbiol Letters. 115. 265-272 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Miyagi,K. et al.: "Successful application of enzyme-1 beled oligonucleotide probe for rapid and accurate cholera-diagnosis in a clinical diagnosis" Microbiology and Immunology. 38. 301-304 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nagayama,K. et al.: "Correlation between cell-associated mannose-sensitive hemagglutination by V.parahaemolyticus and adherence to a human colonic" FEMS Microbiology Letters. 120. 207-210 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shimaoka,M. et al.: "Development of enzyme-labeled oligonucleotide probe for mecA gene in MRSA." Journal of Clincal Microbiology. 32. 1866-1869 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Iijima,Y. et al.: "Simultaneous outbreak due to Vibrio cholerae and Shigella dysenteriae in Kenya." Lancet. 345. 69-70 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoh,M. et al.: "Evaluation of two assay kits for TDH as an indicator of TRH produced by V.parahaemolyticus." Microbiology and Immunology. 39. 157-159 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Honda,T. et al.: "A novel method to chemically immobilize antibodyon nylon and its application to the rapid and diferential detection of two toxins" Clinical and Diagnostic Laboratory Immunology. 2(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 本田,武司: "病気と細菌毒素" 化学同人, 159 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Honda,T.et al.: "The thermostable direct hemolysin of Vibrio parahaemolyticus is a pore-forming toxin" Can.J.Microbiol.38. 1175-1180 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Honda,S.et al.: "A survey of urease-positive V.parahaemolyticus strains isolated from travellers diarrhea…" Eur.J.Epidemiol.8. 861-864 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Honda,T.et al.: "The pathogenicity of V.parahaemolyticus and the role of the thermostable direct hemolysin and related…" Rev.Med.Microbiol.4. 106-113 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoh,M.et al.: "Development of an enzyme-labeled oligonucleotide probe for the cholera toxin gene" J.Clin.Microbiol.31. 1312-1314 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Iida,T.et al.: "Cholera isolates in relation to the “eighth pandemic"" Lancet. 342. 926 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Xu,M.et al.: "Demonstration and characterization of simultaneous production of TDH/I and TRHx by a clinically isolated" Infect.Immun.62. 166-171 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 本田武司 他: "細菌性病原因子研究の基礎的手技と臨床検査への応用" 菜根出版, 210(71-76 101-104 138-140 169-174) (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 本田武司: "病気と細菌毒素" 化学同人, 159 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Naka,A.et al.: "A simple purification method of Vibrio cholerae non-Ol hemagglutinin/protease by immunoaffinity columun chromatography using a monoclonal antibody" Microb.Immunol.36. 419-423 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yoh,M.et al.: "Comparison of Vibrio parahaemolyticus hemolysin(Vp-TRH)produced by environmental and clinical isolates" FEMS Microbiol・Letters. 92. 157-162 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yamamoto,K.et al: "Enzyme-labeled oligonucleotide probes for detection of the genes for thermostable direct hemolysin(TDH) and TDH-related hemolysin(TRH)of Vibrio parahaemolyticus" J.Clin.Microbiol.,. 38. 410-413 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Honda,T.et al.: "The thermostable direct hemolysin of Vibrio parahaemolyticus is a pore-forming toxin." Can.J.Microbiol.38. 1175-1180 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Naka,A et al.: "Characterization of two forms of hemagglutinin/protea produced by Vibrio cholerae non-Ol." FEMS Microbiol.Letters. 98. 197-200 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Honda,T.and T.Iida: "The pathogenicity of Vibrio parahaemolyticus and the role of the thermostable direct hemolysin and related hemolysins" Reviews in Medical Microbiology. 3.

    • Related Report
      1992 Annual Research Report
  • [Publications] 本田 武司: "今日の食中毒" 中央公論社,

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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