• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Pathogenesis of acute encephalopathy accomplished by enterohemorrhagic E. coli infection

Research Project

Project/Area Number 10470072
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

YOSHIDA Shin-ichi  Kyushu University, Department of Bacteriology, Professor, 大学院・医学系研究科, 教授 (60128113)

Co-Investigator(Kenkyū-buntansha) FUJII Jun  University of Occupational and Environmental Health, Department of Microbiology, Assistant Professor, 医学部, 助手 (60271441)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 1999: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1998: ¥9,200,000 (Direct Cost: ¥9,200,000)
KeywordsEHEC / Shiga toxin / acute encephalopathy / pregnancy / verotoxin / antibiotics / 抗毒素療法 / 自律神経 / 血小板凝集
Research Abstract

1. E. coli clones which expressing recombinant Shiga toxin (Stx)1-A and Stx-1-B subunits, were established. Culture supernatant of the clone expressing Stx1-A, nut not Stx1-B showed the inhibitory activity on in vitro protein synthesis. Neither recombinant Stx1-A nor Stx1-B showed Vero cell cytotoxicity. For reconstitution of biologically active toxin, the culture supernatants were mixed. The reconstituted recombinant Stx1 showed both Vero cell cyotoxicity and inhibition in vitro protein synthesis.
2. The therapeutic effect of fosfomycin (FOM), microcycline (MINO), kanamycin (KM) and norfloxacin (NFLX) was evaluated using the EHEC infected mouse model which we established previously. Each of the antimicrobial agents, 1/16 LD50, was given to the mice per os (p.o.) or intraperitoneally (i.p.). For 3 days after bacterial inoculation and then we observed their mortality rate for 2 weeks. The mortality rates of mice administered with MINO (p.o./i.p.), KM (p.o.), NFLX(p.o./i.p) were significantly lower than those of the control group. In an in vitro experiment, each of the four drugs in combination with mitomycin (MMC) caused a more significant decrease in the bacterial number and the release of VT2c than sole MMV.
3. The study was aimed to evaluate the effects of Stx2 on (I) maternal lethality, (ii) fetuses, (iii) delivery period, and (iv) maternal behavior after delivery. Timed pregnant ICR mice were injected intravenously with Stx2 on day 5 of the pregnancy (early stage) or on day 15 (late stage). In early-stage experiments, the number of normal fetuses of mic injected with Stx2 was significantly lower than that of control mice. In late-stage experiments, mothers injected with Stx2 delivered normal numbers of neonates, but could not take care of them. The lethal dose of Stx2 were not difficult for pregnant and nonpregnant female mice at either stage.

Report

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

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Nishikawa T. et al: "Reconstitution of active recombinant Shiga toxin (Stx) 1 from recombinant Stx1-A and Stx1-B subunits independently produced by E. coli clones."FEMS Microbiology Letters. 178. 13-18 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshimura K. et al: "Cheemotherapy for enterohemorrhagic Escherchia coli O157:H-infection in a mouse model."FEMS Immunology and Medical Microbology. 26(2). 101-108 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshimura K. et al: "Effects of Shiga toxin 2 on the lethality, featuses, delivery and puperperal behavior of pregnant mice."Infection and Immunity. 68. 000-000 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishikawa T., Fujii J., Yoshida S., and Yutsudo T.: "Reconstitution of active recombinant Shira toxin (Stx)1 from recombinant Stx1-A and Stx1-B subunits independently produced by E. coli clones"FEMS Microbiology Letters. 178. 13-18 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshimura K., Fujii J., Taniguchi H., and Yoshida S.: "Chemotherapy for enterohemorrhagic Escherichia coli O157 : H- injection in a mouse model"FEMS Immunology and Medical Microbiology. 26(2). 101-108 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshimura K., Fujii J., Tanimoto A., Yutsuda T., Kashimura M., and Yoshida S.: "Effects of Shiga toxin 2 on the lethality, fetuses, delivery and puerperal behavior of pregnant mice"Infection and Immunity. 68. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishikawa T. et al: "Reconstitution of active recombinant Shiga toxin (Stx)1 from recombinant Stx1-A and Stx1-B subunits independently produced by E.coli clones."FEMS Microbiology Letters. 178. 13-18 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshimura K. et al: "Chemotherapy for enterohemorrhagic Escherichia coli O157:H-infection in a mouse model."FEMS Immunology and Medical Microbiology. 26(2). 101-108 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshimura K. et al: "Effects of Shiga toxin 2 on the lethality, fetuses, delivery and puerperal behavior of pregnant mice."Infection and Immunity. 68. 000-000 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamada Y et al: "Brainstem mechanisms of autonomic dysfunction in the encephalopathy-associated Shiga toxin 2 intoxication." Annals of Neurology. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fujii J et al: "Neurotoxicity of intrathecal Shiga toxin 2 and protection by intrathecal injection of anti-Shiga toxin 2 antiserum in rabbits." Microbial Pathogenesis. 25. 139-146 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshimura K et al: "No direct effects of Shiga toxin 1 and 2 on the aggregation of human platelets in vitro." Thrombosis and Haemostasis. 80. 529-530 (1998)

    • Related Report
      1998 Annual Research Report

URL: 

Published: 1998-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi