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Functional analyses of the type III effectors in pathogenic E.coli

Research Project

Project/Area Number 16590370
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

ABE Akio  Kitasato University, Kitasato Institute for Life Sciences, Professor, 北里生命科学研究所, 教授 (50184205)

Co-Investigator(Kenkyū-buntansha) KUWAE Asaomi  Kitasato University, Kitasato Institute for Life Sciences, Assistant professor, 北里生命科学研究所, 講師 (60337996)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsEnteropathogenic E.coli / Enterohemorrhagic E.coli / Type III secretion system / Diarrhea / Effector / Microtuble / GEF-H1 / Tight junction / アクチン / GFF-H1
Research Abstract

Enteropathogenic Escherichia coli delivers a subset of effectors into host cells via a type III secretion system, and this step is required for the progression of disease. In this study, we demonstrated that the type III effectors, EspG and its homolog EspG2, trigger actin stress fiber formation and the destruction of the microtubule networks beneath adherent bacteria. Both effectors were shown to possess the ability to interact with tubulins, and to stimulate microtubule destabilization in vitro. A recent study showed that microtubule-bound GEF-H1, a RhoA-specific guanine nucleotide exchange factor, was converted to its active form by microtubule destabilization, and this sequence of events resulted in RhoA stimulation. Indeed, EspG- and EspG2-induced stress fiber formation was inhibited by the expression of dominant-negative forms of GEF-H1 and RhoA, but not of Rac1 and Cdc42. These results indicate that the impact of EspG/EspG2 on microtubule networks triggers the activation of the … More RhoA-ROCK signaling pathway via GEF-H1 activity. In addition, we revealed that the EspG/EspG2 alter epithelial paracellular permeability. When MDCK cells were infected with wild-type (WT) EPEC, RhoA was activated, and this event was dependent on the delivery of either EspG or EspG2 into host cells. In contrast, a loss of transepithelial electrical resistance and ZO-1 disruption were induced by infection with an espG/espG2 double-knockout mutant, as was the case with the WT EPEC, indicating that EspG/EspG2 is not involved in the disruption of tight junctions during EPEC infection. Although EspG- and EspG2-expressing MDCK cells exhibited normal overall morphology and maintained fully assembled tight junctions, the paracellular permeability to 4-kDa dextran, but not the paracellular permeability to 500-kDa dextran, was greatly increased. This report reveals for the first time that a pathogen can regulate the size-selective paracellular permeability of epithelial cells in order to elicit a disease process. Less

Report

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

    (24 results)

All 2006 2005 2004

All Journal Article (24 results)

  • [Journal Article] Assembly of the type III secretion apparatus of enteropathogenic Escherichia coli2006

    • Author(s)
      Tomoaki Ogino
    • Journal Title

      J. Bacteriology 188・8

      Pages: 2801-2811

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] BopC is a novel type III effector secretes by Bordetella bronchiseptica and has a critical role in type III-dependent necrotic cell death2006

    • Author(s)
      Asaomi Kuwae
    • Journal Title

      J. Bio1. Chem. 281・10

      Pages: 6589-6600

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Assembly of the type III secretion apparatus of enteropathogenic Escherichia coli2006

    • Author(s)
      Tomoaki Ogino
    • Journal Title

      J.Bacteriology 188(8)(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] BopC is a novel type III effector secreted by Bordetella bronchiseptica and has a critical role in type III-dependent necrotic cell death2006

    • Author(s)
      Asaomi Kuwae
    • Journal Title

      J.Biol.Chem. 281(10)

      Pages: 6589-6600

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Assembly of the type III secretion apparatus of enteropathogenic Escherichia coli2006

    • Author(s)
      Tomoaki Ogino
    • Journal Title

      J.Bacteriology 188・8(In Press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] BopC is a novel type III effector secreted by Bordetella bronchiseptica and has a critical role in type III-dependent necrotic cell death2006

    • Author(s)
      Asaomi Kuwae
    • Journal Title

      J.Biol.Chem. 281・10

      Pages: 6589-6600

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Enteropathogenic Escherichia coli type III effectors EspG and EspG2 alter epithelial paracellular permeability2005

    • Author(s)
      Takeshi Matsuzawa
    • Journal Title

      Infect. Immun. 73・10

      Pages: 6283-6289

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enteropathogenic Escherichia coil activates the RhoA signaling pathway via the stimulation of GEF-H12005

    • Author(s)
      Takeshi Matsuzawa
    • Journal Title

      EMBO J. 23・17

      Pages: 3570-3582

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Type-III effectors : Sophisticated bacterial virulence factors2005

    • Author(s)
      Akio Abe
    • Journal Title

      Comptes Rendus Biologies 328・5

      Pages: 413-428

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enteropathogenic Escherichia coli type III effectors EspG and EspG2 alter epithelial paracellular permeability2005

    • Author(s)
      Takeshi Matsuzawa
    • Journal Title

      Infect.Immun. 73(10)

      Pages: 6283-6289

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enteropathogenic Escherichia coli activates the RhoA signaling pathway via the stimulation of GEF-H12005

    • Author(s)
      Takeshi Matsuzawa
    • Journal Title

      EMBO J. 23(17)

      Pages: 3570-3582

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Type-III effectors : Sophisticated bacterial virulence factors2005

    • Author(s)
      Akio Abe
    • Journal Title

      Comptes Rendus Biologies 328(5)

      Pages: 413-428

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 細菌のIII型分泌装置とその機能2005

    • Author(s)
      桑江 朝臣
    • Journal Title

      化学療法の領域 21・5

      Pages: 27-33

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 腸管病原性大腸菌の感染機構2005

    • Author(s)
      阿部章夫
    • Journal Title

      実験医学 23・17

      Pages: 2618-2624

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Binding of intimin with Tir on the bacterial surface is prerequisite for the barrier disruption induced by enteropathogenic Escherichia coli2005

    • Author(s)
      Masami Miyake
    • Journal Title

      BBRC 337・3

      Pages: 922-927

    • Related Report
      2005 Annual Research Report
  • [Journal Article] グラム陰性菌の分泌装置2005

    • Author(s)
      阿部 章夫
    • Journal Title

      Helicobacter Research 9・2

      Pages: 2-9

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 病原細菌のリーサルウェポン"III型分泌装置"2005

    • Author(s)
      桑江朝臣
    • Journal Title

      蛋白質核酸酵素 50・1

      Pages: 20-28

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Targeting of enteropathogenic Escherichia coli EspF to host mitochondria is essential for bacterial pathogenesis2005

    • Author(s)
      Takeshi Nagai
    • Journal Title

      Journal of Biological Chemistry 280・4

      Pages: 2998-3011

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Type III effectors : Sophisticated bacterial virulence factors2005

    • Author(s)
      Akio Abe
    • Journal Title

      Comptes Rendus BIOLOGIES (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The type III secreted protein, BopD, in Bordetella bronchiseptica is complexed with BopB for pore formation on the host plasma membrane.2004

    • Author(s)
      Hisashi Nogawa
    • Journal Title

      J. Bacteriology 186・12

      Pages: 3806-3813

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The type III secreted protein, BopD, in Bordetella bronchiseptica is complexed with BopB for pore formation on the host plasma membrane.2004

    • Author(s)
      Hisashi Nogawa
    • Journal Title

      J.Bacteriology 186(12)

      Pages: 3806-3813

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 蛋白質輸送:病原細菌エフェクターの宿主細胞への旅立ち2004

    • Author(s)
      阿部章夫
    • Journal Title

      蛋白質核酸酵素 49・7

      Pages: 967-970

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The type III secreted protein, BopD, in Bordetella bronchiseptica is complexed with BopB for pore formation on the host plasma membrane2004

    • Author(s)
      Hisashi Nogawa
    • Journal Title

      Journal of Bacteriology. 186・12

      Pages: 3806-3813

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Enteropathogenic Escherichia coli activates the RhoA signaling pathway via the stimulation of GEF-H12004

    • Author(s)
      Takeshi Matsuzawa
    • Journal Title

      The EMBO Journal 23・17

      Pages: 3570-3582

    • Related Report
      2004 Annual Research Report

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

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