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The studies of Helicobacter pylori on the functions of effector protein and the mechanisms of gastric mucosa infection.

Research Project

Project/Area Number 15390141
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionThe University of Tokyo

Principal Investigator

SASAKAWA Chihiro  The University of Tokyo, The Institute of Medical Science, Professor, 医科学研究所, 教授 (70114494)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 2003: ¥7,900,000 (Direct Cost: ¥7,900,000)
KeywordsHelicobacter pylori / Pathogenicity / Stomach / Secretion system / CagA
Research Abstract

1.To investigate the type IV secretion system (TFSS) apparatus on the surface of Helicobacter pylori, we focused on Cag-related proteins such as Hp0532 (VirB7), Hp0528 (VirB9) and Hp0527 (VirB10), since the proteins were all postulated to be associated with the outer membrane based on the localization of the corresponding homologous proteins of the TFSS of Agrobactenum tumefaciens. To investigate the protein localization in H.pylori, we prepared polyclonal antibodies against each of the Cag proteins. The filamentous structures on bacterium were found to be associated with the major components of TFSS by immunofluorescence and immunogold electron microscopy. Our results thus provide for the first time direct evidence that the H.pylori TFSS apparatus is a filamentous macromolecular complex protruding from the bacterial envelope [Cell.Microbiol.(2003) 5, 395-404].
2.H.pylori deliver the CagA protein into host cells and are associated with peptic ulcer disease and gastric carcinoma. Injecte … More d CagA targets several host proteins including Grb2, SHP-2 and Csk, that are linked to changes in the structure and function of gastric epithelial cells. We identified that CagA binds Crk adaptor proteins, and its interaction plays a critical role in promoting cell scattering. The responses induced by H.pylori infection were significantly diminished when blocked Crk function by the over expression of dominant negative Crk or by the knockdown of endogenous Crk with RNAi treatment. The similar inhibitory effects were also observed when inhibited H-Ras, Rap1 or Rac1 involving in downstream of Crk signaling. Thus, the versatile Crk-mediated CagA activity can commit various signaling pathways in gastric epithelium.
3.We investigated the apoptosis of gastric epithelial cells infected with H, pylori and found that CagA that were injected into the host cell could prevent the infected cells from apoptosis. By using the various kinase inhibitors and siRNA techniques, it was suggested that the MAPK activation of infected cells by CagA could associate with the inhibitory effects of apoptosis.
These data suggest that CagA protein could induce the up regulation of signal cascade of the infected cells during long-term H.pylori infection, that would be unbalanced programd cell death and proliferation of the normal gastric cells, leading to the onset and malignancy of various gastric diseases. Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (24 results)

All 2005 2004 2003 Other

All Journal Article (21 results) Publications (3 results)

  • [Journal Article] Targeting of enteropathogenic Escherichia coli EspF to host mitochondria is essential for the bacterial pathogenesis : critical role of the 16th leucine residue in EspF.2005

    • Author(s)
      Nagai, T. et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 2998-3011

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Type IV secretion system in Helicobacter pylori : comparison with bacterial type III secretion apparatus.2005

    • Author(s)
      Tanaka, J. et al.
    • Journal Title

      Tanpakushitsu Kakusan Koso 50

      Pages: 36-43

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Type IV secretion system in Helicobacter pylori : comparison with bacterial type III secretion apparatus.2005

    • Author(s)
      Tanaka, J. et al.
    • Journal Title

      Tanpakushitsu Kakusan Koso. 50

      Pages: 36-43

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Targeting of enteropathogenic Escherichia coli EspF to host mitochondria is essential for bacterial pathogenesis : critical role of the 16th leucine residue in EspF.2005

    • Author(s)
      Nagai, T.
    • Journal Title

      The Journal of Biological Chemistry 280・4

      Pages: 2998-3011

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Escape of intracellular Shigella from autophagy.2005

    • Author(s)
      Ogawa, M.
    • Journal Title

      Science 307・5710

      Pages: 727-731

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ピロリ菌のIV型分泌機構-III型分泌装置との比較2005

    • Author(s)
      Tanaka, J.
    • Journal Title

      蛋白質核酸酵素 50・1

      Pages: 36-43

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A novel caspase-1/Toll-like receptor 4-independent pathway of Cell death induced by cytosolic Shigella in infected macrophages.2005

    • Author(s)
      Suzuki, T.
    • Journal Title

      The Journal of Biological Chemistry 280

      Pages: 14042-14050

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Intestinal villous M cells : an antigen entry site in the mucosal epithelium.2004

    • Author(s)
      Jang, M.H.et al.
    • Journal Title

      Proc Natl Acad Sci U S A 101

      Pages: 6110-6115

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel in vitro infection model of Helicobacter pylori using mucin-producing murine gastric surface mucous cells.2004

    • Author(s)
      Takahashi, T. et al.
    • Journal Title

      Helicobacter 9

      Pages: 302-312

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Intestinal villous M cells : an antigen entry site in the mucosal epithelium.2004

    • Author(s)
      Jang, M.H.et al.
    • Journal Title

      Proc Natl Acad Sci U S A 101・16

      Pages: 6110-6115

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A novel in vitro infection model of Helicobacter pylori using mucin-producing murine gastric surface mucous cells.2004

    • Author(s)
      Takahashi, T.
    • Journal Title

      Helicobacter 9・4

      Pages: 302-312

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Enteropathogenic Escherichia coli activates the RhoA signaling pathway via the stimulation of GEF-H1.2004

    • Author(s)
      Matsuzawa, T.
    • Journal Title

      The EMBO Journal 23・17

      Pages: 3570-3582

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Structural definition on the surface of Helicobacter pylori type IV secretion apparatus.2003

    • Author(s)
      Tanaka, J. et al.
    • Journal Title

      Cell.Microbiol. 5

      Pages: 395-404

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hyper Adherence to Caco-2 Cells Caused by Disruption of yhiE and yhiF Genes in Enterohemorrhagic Escherichia coli O157:H7.2003

    • Author(s)
      Tatsuno, I. et al.
    • Journal Title

      Infect.Immun. 71

      Pages: 2598-2606

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Distribution of the secondary type III secretion system locus found in enterohemorrahagic Escherichia coli O157:H7 among Shiga toxin-producing E. coli.2003

    • Author(s)
      Makino, S. et al.
    • Journal Title

      J.Clin.Microbiol. 41

      Pages: 2341-2347

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Helicobacter pylori induces RANTES through activation of NF-kappa B.2003

    • Author(s)
      Mori, N. et al.
    • Journal Title

      Infect.Immun. 71

      Pages: 3748-3756

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Role of microfilaments and microtubules in the invasion of INT-407 cells by Campylobacter jejuni2003

    • Author(s)
      Biswas, D. et al.
    • Journal Title

      Microbiol Immunol 47

      Pages: 469-473

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Structural definition on the surface of Helicobacter pylori type N secretion apparatus.2003

    • Author(s)
      Tanaka, J. et al.
    • Journal Title

      Cell.Microbiol. 5

      Pages: 395-404

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hyper Adherence to Caco-2 Cells Caused by Disruption of yhiE and yhiF Genes in Enterohemorrhagic Escherichia coli O157 : H7.2003

    • Author(s)
      Tatsuno, I. et al.
    • Journal Title

      Infect.Immun. 71

      Pages: 2598-2606

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Distribution of the secondary type III secretion system locus found in enterohemorrahagic Escherichia coil O157 : H7 among Shiga toxin-producing E.coli.2003

    • Author(s)
      Makino, S. et al.
    • Journal Title

      J.Clin.Microbiol. 41

      Pages: 2341-2347

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Role of microfilaments and microtubules in the invasion of INT-407 cells by Campylobacter jejuni.2003

    • Author(s)
      Biswas, D. et al.
    • Journal Title

      Microbiol Immunol. 47

      Pages: 469-473

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Mori, N., Krensky, A.M., Geleziunas, R., Wada, A., Hirayama, T., Sasakawa, C., Yamamoto, N.: "Helicobacter pylori induces RANTES through activation of NF-κB"Infection and Immunity. 71・7. 3748-3756 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 三室 仁美, 笹川 千尋: "Helicobacter pyloriのvirulence factor - cag PAIをめぐる最近の知見-CagAの活性とGrb2"Helicobacter Research. 7. 37-45 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tanaka, J., Suzuki, T., Mimuro, H., Sasakawa, C.: "Structural definition on the surface of Helicobacter pylori IV secretion apparatus"Cellular Microbiology. 5・6. 395-404 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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