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Genome Analysis of Emergence Mechanisms of New Enterohemorrhagic Escherichia coli and Genome-Based Drug Research toward HUS Treatment

Research Project

Project/Area Number 16390128
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

YAMAMOTO Tatsuo  Niigata University, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (80095843)

Co-Investigator(Kenkyū-buntansha) TANEIKE Ikue  Niigata University, Faculty of Medicine, Assistant Teacher, 医学部, 教務補佐員 (50397105)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2005: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2004: ¥9,300,000 (Direct Cost: ¥9,300,000)
KeywordsEnterohemorrhagic Escherichia coli (EHEC) / HUS / Genome analysis / WIM model / Adherence factor / IgA1 protease / 腸管出血性大腸菌(EHEC) / 溶血性尿毒症症候群(HUS) / タイプIII分泌システム / 血清型O86 / 粘着性プラスミド / 志賀毒素ファージ / アニソダミン
Research Abstract

Infection of children and the elderly with enterohemorrhagic Escherichia coli (EHEC) results in hemolytic uremic syndrome (HUS), a severe complication with a poor prognosis. The type III secretion system (mechanism of intestinal colonization) of EHEC has been considered to be essential for the development of HUS. However, in case of intrafamilinal infection due to serotype O86 EHEC, although the E.coli strains do not have the type III secretion system, infected children developed HUS, and died. In this study, we investigated the molecular genetic properties of serotype O86 EHEC strains. These strains had a 120.73-kb plasmid (pO86A) encoding a diffuse adherence factor (HdaA), and lysogenized a 60.238-kb phage encoding type 2 Shiga toxin (Stx2). pO86A also had the Shigella flexneri type IgA1 protease gene, and conferred resistance to mucosal immunity to serotype O86 EHEC strains. The Stx phage showed properties of the insertion site found only in O86 strains, but not in O157 strains. These results support the hypothesis that in the intestinal tract of a child, serotype O86-specific Stx2 phage is lysogenized into highly-colonizing (diffusely-adhering and IgA1 protease-producing) O86 E.coli strains, resulting in the emergence of new EHEC, causing fatal HUS. It was also concluded that type III secretion is not essential for the development of HUS. Moreover, it is considered that Shiga toxin induces inflammatory cytokines such as IL-6 and IL-8 to cause HUS. We demonstrated that a Chinese herb, anisodamine, and an antimicrobial agent, azityhromycin, inhibited such an inflammatory cytokine induction, most probably blocking the NF-kB activation pathway.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (21 results)

All 2006 2005 2004

All Journal Article (20 results) Book (1 results)

  • [Journal Article] Change in the bacterial flora of pouchitis.2006

    • Author(s)
      Iwaya A, Iiai T, Okamoto H, Ajioka Y, Yamamoto I, Asahara T, Nomoto K, Hatakeyama K
    • Journal Title

      Hepatogastroenterology 53(67)

      Pages: 55-59

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 小児腸管出血性大腸菌感染症とその発症メカニズム2006

    • Author(s)
      山本達男
    • Journal Title

      新潟医学会雑誌 (印刷中)

    • NAID

      110006483495

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Change in the bacterial flora of pouchitis.2006

    • Author(s)
      Iwaya A, liai T, Okamoto H, Ajioka Y, Yamamoto T, Asahara T, Nomoto K, Hatakeyama K
    • Journal Title

      Hepatogastroenterology 53(67)

      Pages: 55-59

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Childfood enterohemorrhagic Escherichia coli infection and its mechanism2006

    • Author(s)
      Yamamoto T
    • Journal Title

      Niigata Med.J. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Change in the bacterial flora of pouchitis.2006

    • Author(s)
      Iwaya A, Iiai T, Okamoto H, Ajioka Y, Yamamoto T, Asahara T, Nomoto K, Hatakeyama K
    • Journal Title

      Hepatogastroenterology 53(67)

      Pages: 55-59

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Specific Inhibitory Action of Anisodamine against a Staphylococcal Super antigenic Toxin, Toxic Shock Syndrome Toxin (TSST)-1, Leading to Down-Regulation of Cytokine Production and Blockin of TSST-1 Toxicity in Mice.2005

    • Author(s)
      Nakagawa S, Kushiya K, Taneike I, Imanishi K, Uchiyama T, Yamamoto T
    • Journal Title

      Clin. Diag. Lab. Immunol. 12(3)

      Pages: 399-408

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene sequences and specific detection for Panton-Valentine leukocidin.2005

    • Author(s)
      Nakagawa S, Taneike I, Mimura D, Iwakura N, Nakayama T, Emura T, Kitatsuji M, Fujimoto A, Yamamoto T
    • Journal Title

      Biochem. Biophys. Res. Commun. 328(4)

      Pages: 955-1002

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A Panton-Valentine leukocidin (PVL)-positive community-acquired methicillin-resistant Staphylococcus aureus (MRSA) strain, another such strain carrying a multiple-drug resistance plasmid, and other more-typical PVL-negative strains found in Japan.2005

    • Author(s)
      Takizawa Y, Taneike I, Nakagawa S, Oishi T, Nitahara Y, Iwakura N, Ozaki K, Takano M, Nakayama T, Yamamoto T
    • Journal Title

      J. Clin. Microbiol 43(7)

      Pages: 3356-3363

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rapid and quantitative detection of blood Serratia marccscens by a real-time PCR assay: its clinical application and evaluation in a mouse infection model.2005

    • Author(s)
      Iwaya A, Nakagawa S, Iwakura N, Taneike I, Kurihara M, Kuwano T, Gondaira F, Endo M, Hatakeyama K, Yamamoto T
    • Journal Title

      FEMS Microbiol. Lett. 248(2)

      Pages: 163-170

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Specific Inhibitory Action of Anisodamine against a Staphylococcal Superantigenic Toxin, Toxic Shock Syndrome Toxin (TSST)-1, Leading to Down-Regulation of Cytokine Production and Blocking of TSST-1 Toxicity in Mice.2005

    • Author(s)
      Nakagawa S, Kushiya K, Taneike I, Imanishi K, Uchiyama T, Yamamoto T
    • Journal Title

      Clin.Diag.Lab.Immunol. 12(3)

      Pages: 399-408

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Gene sequences and specific detection for Panton-Valentine leukocidin.2005

    • Author(s)
      Nakagawa S, Taneike I, Mimura D, Iwakura N, Nakayama T, Emura T, Kitatsuji M, Fujimoto A, Yamamoto T
    • Journal Title

      Biochem.Biophys.Res.Commun. 328(4)

      Pages: 995-1002

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] A Panton-Valentine leukocidin (PVL)-positive community-acquired methicillin-resistant Staphylococcus aureus (MRSA) strain, another such strain carrying a multiple-drug resistance plasmid, and other more-typical PVL-negative strains found in Japan.2005

    • Author(s)
      Takizawa Y, Taneike I, Nakagawa S, Oishi T, Nitahara Y, Iwakura N, Ozaki K, Takano M, Nakayama T, Yamamoto T
    • Journal Title

      J.Clin.Microbiol 43(7)

      Pages: 3356-3363

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Rapid and quantitative detection of blood Serratia marcescens by a real-time PCR assay : its clinical application and evaluation in a mouse infection model.2005

    • Author(s)
      Iwaya A, Nakagawa S, Iwakura N, Taneike I, Kurihara M, Kuwano T, Gondaira F, Endo M, Hatakeyama K, Yamamoto T
    • Journal Title

      FEMS Microbiol.Lett. 248(2)

      Pages: 163-170

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rapid and quantitative detection of blood Serratia marcescens by a real-time PCR assay : its clinical application and evaluation in a mouse infection model.2005

    • Author(s)
      Iwaya A, Nakagawa S, Iwakura N, Taneike I, Kurihara M, Kuwano T, Gondaira F, Endo M, Hatakeyama K, Yamamoto T
    • Journal Title

      FEMS Microbiol. Lett. 248(2)

      Pages: 163-170

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Gene sequences and specific detection for Panton-Valentine leukocidin2005

    • Author(s)
      S.Nakagawa
    • Journal Title

      Biochemical and Biophysical Research Communications 328(4)

      Pages: 995-1002

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Specific Inhibitory Action of Anisodamine against a Staphylococcal Superantigenic Toxin, Toxic Shock Syndrome Toxin(TSST)-1, Leading to Down-Regulation of Cytokine Production and Blocking of TSTT-1 Toxicity in Mice2005

    • Author(s)
      S.Nakagawa
    • Journal Title

      Clinical and Diagnostic Laboratory Immunology 12(3)

      Pages: 399-408

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Study on the Regulation and Energy Requirements of Helicobacter pylori Motility and Its Inhibitors2004

    • Author(s)
      K.Kushiya
    • Journal Title

      Acta Medica et Biologica 52

      Pages: 133-140

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Colonization Behavior of the Virulent Genotypes of Helicobacter pylori, a Bacterial Risk Factor for Gastric Cancer, in the Human Gastric Mucosa : a Case Study from an Intrafamilial Infection2004

    • Author(s)
      I.Taneike
    • Journal Title

      Far Eastern International Pacific Medical Journal(Russia) 2

      Pages: 94-96

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Intrafamilial Spread of the Same Clarithromycin-Resistant Helicobacter pylori Infection Confirmed by Molecular Analysis2004

    • Author(s)
      I.Taneike
    • Journal Title

      Journal of Clinical Microbiology 42

      Pages: 3901-3903

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Panton-Valentine leukocidin positive community-acquired MRSA infection in Japan2004

    • Author(s)
      T.Yamamoto
    • Journal Title

      Eurosurveillance Weekly 8(7)

      Pages: 6-7

    • Related Report
      2004 Annual Research Report
  • [Book] 日露学術交流Handbook2005

    • Author(s)
      山本 達男
    • Publisher
      山本達男(印刷中)
    • Related Report
      2004 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

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