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

Elucidation of the pathogenic reinforcement action of enterohemorrhagic Escherichia coli produced SubAB

Research Project

Project/Area Number 24390104
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionChiba University

Principal Investigator

Noda Masatoshi  千葉大学, 医学(系)研究科(研究院), 教授 (60164703)

Co-Investigator(Kenkyū-buntansha) 清水 健  千葉大学, 医学(系)研究科(研究院), 准教授 (70312840)
八尋 錦之助  千葉大学, 医学(系)研究科(研究院), 准教授 (80345024)
津々木 博康  大阪府立大学, 理学(系)研究科(研究院), 助教 (40586608)
小倉 康平  千葉大学, 大学院・医学研究院, 特任研究院 (00586612)
Project Period (FY) 2012-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2014: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords腸管出血性大腸菌 / SubAB / 小胞体ストレス / 一酸化窒素 / 細胞死 / ストレスグラニュール / 志賀毒素 / 酸化ストレス / lipid-raft / 毒素 / オートファジー / 取り込み機構 / 阻害剤 / lipid-raft / NO
Outline of Final Research Achievements

Subtilase cytotoxin (SubAB) is mainly produced by locus of enterocyte effacement (LEE) -negative strains of Shiga-toxigenic Escherichia coli (STEC). SubAB cleaves an endoplasmic reticulum (ER) chaperone, BiP/Grp78, leading to induction of ER stress. This stress causes activation of ER stress sensor proteins and induction of apoptosis. Here we showed that 1) SubAB enters the cells via lipid rafts- and an actin-dependent pathways 2)in mouse macrophages, that SubAB inhibited LPS-stimulated NO production through inhibition of NF-kB nuclear translocation and iNOS expression 3)SubAB-induced SG formation is regulated by the PERK/DAP1 signaling pathway, which may be modulated by PKCdelta/PKD1.

Report

(6 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (45 results)

All 2017 2016 2015 2014 2013 2012 Other

All Journal Article (17 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 1 results,  Acknowledgement Compliant: 4 results) Presentation (27 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results) Book (1 results)

  • [Journal Article] Nitric oxide-enhanced Shiga toxin production was regulated by Fur and RecA in enterohemorrhagic Escherichia coli O157.2017

    • Author(s)
      K. Ichimura, Shimizu. T, Takeuchi. H, Matsumoto. A, Yahiro. K, Noda. M,
    • Journal Title

      MicrobiologyOpen

      Volume: 印刷中 Issue: 4 Pages: 1-17

    • DOI

      10.1002/mbo3.461

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The surface sensor NlpE of enterohemorrhagic Escherichia coli contributes to regulation of the type III secretion system and flagella by the Cpx response to adhesion2016

    • Author(s)
      Takeshi Shimizu, Kimitoshi Ichimura and Masatoshi Noda
    • Journal Title

      Infect. Immun.

      Volume: 84 Issue: 2 Pages: 537-549

    • DOI

      10.1128/iai.00881-15

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Subtilase cytotoxin produced by locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli induces stress granule formation2016

    • Author(s)
      H. Tsutsuki, K. Yahiro, K. Ogura, K. Ichimura, S. Iyoda, M. Ohnishi, S. Nagasawa, K. Nagasawa, J. Moss, M. Noda
    • Journal Title

      Cellular Microbiology

      Volume: -

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Translation from the 5' untranslated region shapes the integrated stress response2016

    • Author(s)
      Starck SR, Tsai JC, Chen K, Shodiya M, Wang L, Yahiro K, Martins-Green M, Shastri N, Walter P.
    • Journal Title

      Science

      Volume: 351 Issue: 6272

    • DOI

      10.1126/science.aad3867

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 腸管出血性大腸菌感染症の現状と病原性2016

    • Author(s)
      八尋錦之助、野田公俊
    • Journal Title

      化学療法の領域

      Volume: 32 Pages: 70-76

    • Related Report
      2015 Annual Research Report
  • [Journal Article] DAP1, a Negative Regulator of Autophagy, Controls SubAB-Mediated Apoptosis and Autophagy2014

    • Author(s)
      Yahiro, K. Tsutsuki, H. Ogura, K. Nagasawa, S. Moss, J. Noda, M.
    • Journal Title

      Infect Immun

      Volume: 82 Issue: 11 Pages: 4899-4908

    • DOI

      10.1128/iai.02213-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Uptake of Shiga-toxigenic Escherichia coli SubAB by HeLa cells requires an actin- and lipid raft-dependent pathway2014

    • Author(s)
      Nagasawa, S. Ogura, K. Tsutsuki, H. Saitoh, H. Moss, J. Iwase, H. Noda, M. Yahiro, K.
    • Journal Title

      Cell Microbiol

      Volume: 16 Issue: 10 Pages: 1582-1601

    • DOI

      10.1111/cmi.12315

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 腸管出血性大腸菌による食中毒重症化メカニズム2013

    • Author(s)
      清水 健、野田 公俊
    • Journal Title

      日本医事新報

      Volume: 4614 Pages: 98-99

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 病原細菌のAB5型トキシンの作用機構等に関する研究2013

    • Author(s)
      野田 公俊
    • Journal Title

      日本細菌学雑誌

      Volume: 68 Pages: 299-311

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Large-scale preparation of Shiga toxin 2 in Escherichia coli for toxoid vaccine antigen production2013

    • Author(s)
      Hideyuki Arimitsu, Keiko Sasaki, Takeshi Shimizu, Kentaro Tsukamoto,
    • Journal Title

      Microbiol. Immunol.

      Volume: 57 Pages: 38-45

    • NAID

      40019554365

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 腸管出血性大腸菌の重症化要因2013

    • Author(s)
      清水 健、野田 公俊
    • Journal Title

      感染・炎症・免疫

      Volume: 43 Pages: 74-76

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Large - scale preparation of Shiga toxin 2 1n Escherichia coli for toxoid vaccine antigen production.2013

    • Author(s)
      Hideyuki Arimitsu, Keiko Sasaki, Takeshi Shimizu, Kentaro Tsukamoto, Toshiyasu Shimizu and Takao Tsuji
    • Journal Title

      Microbiol. Immunol.

      Volume: 57 Issue: 1 Pages: 38-45

    • DOI

      10.1111/j.1348-0421.2012.12004.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Subtilase cytotoxin enhances Escherichia coli survival in macrophages by suppression of nitric oxide production through the inhibition of NF-κB activation2012

    • Author(s)
      Tsutsuki H, Yahiro K, Suzuki K, Suto A, Ogura K, Nagasawa S, Ihara H, Shimizu T, Nakajima H, Moss J, Noda M
    • Journal Title

      Infect Immun

      Volume: 80 Issue: 11 Pages: 3939-51

    • DOI

      10.1128/iai.00581-12

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 腸管出血性大腸菌の病原性発現機構2012

    • Author(s)
      八尋錦之助
    • Journal Title

      化学療法の領域

      Volume: 28 Pages: 45-52

    • Related Report
      2012 Annual Research Report
  • [Journal Article] The nitric oxide reductase of enterohemorrhagic Escherichia coli plays an important role for the survival within macrophages2012

    • Author(s)
      Shimizu T, Tsutsuki H, Matsumoto A, Nakaya H, Noda M
    • Journal Title

      Mol Microbiol

      Volume: 85 Issue: 3 Pages: 492-512

    • DOI

      10.1111/j.1365-2958.2012.08122.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recombinant Shiga toxin B subunit can induce neutralizing immunoglobulin Y antibody.2012

    • Author(s)
      Paola Neri, Shunji Tokoro, Tsuyoshi Sugiyama, Kouji Umeda, Takeshi Shimizu, Takao Tsuji, Yoshikatsu Kodama and Hiroshi Mori
    • Journal Title

      Biol. Pharm. Bull.

      Volume: 35 Pages: 917-923

    • NAID

      130001872174

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 腸管出血性大腸菌による食中毒重症化メカニズム2012

    • Author(s)
      清水 健、野田公俊
    • Journal Title

      日本医事新報

      Volume: 4614 Pages: 98-99

    • Related Report
      2012 Annual Research Report
  • [Presentation] 腸管出血性大腸菌 O157が保持する新規病原因子一酸化窒素還元酵素遺伝子norVの進化的解析2016

    • Author(s)
      清水健、平井晋一郎、横山栄二、市村公敏、野田公俊
    • Organizer
      第89回日本細菌学会
    • Place of Presentation
      大阪府大阪市天王寺区
    • Year and Date
      2016-03-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腸管出血性大腸菌Subtilase cytotoxinによるインフラマーソム抑制機構の解析2016

    • Author(s)
      津々木博康、ThianliZhang,小野勝彦、八尋錦之助、澤智裕、野田公俊
    • Organizer
      第89回日本細菌学会
    • Place of Presentation
      大阪
    • Year and Date
      2016-03-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 一酸化窒素による腸管出血大腸菌の志賀毒素産生亢進機構の解析2016

    • Author(s)
      市村公敏、清水健、八尋錦之助、竹内裕紀、野田公俊
    • Organizer
      第89回日本細菌学会
    • Place of Presentation
      大阪府大阪市天王寺区
    • Year and Date
      2016-03-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of Shiga-toxigenic Escherichia coli-produced Subtilase cytotoxin(SubAB)on host cells2016

    • Author(s)
      Yahiro, K.
    • Organizer
      Invitation meeting
    • Place of Presentation
      NIH/NHLBI, Bethesda,USA
    • Year and Date
      2016-01-14
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] An evolutionary analysis of a novel virulence gene norV that encodes nitric oxide reductase in enterohemorrhagic Escherichia coli O1572016

    • Author(s)
      Takeshi Shimizu,Shinichiro Hirai,Eiji Yokoyama, Kimitoshi Ichimura ando Masatoshi Noda
    • Organizer
      50th Joint Conference on Cholera and Other Bacterial Enteric Infections Panel
    • Place of Presentation
      Bethesda, USA
    • Year and Date
      2016-01-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Shiga-toxigenic Escherichia coli SubAB-induced ER stress causes stress granule formation in mammalian cells2016

    • Author(s)
      Yahiro, K., H. Tsutsuki, K. Ogura, S. Iyoda, K. Ichimura, T. Shimizu, M. Ohnishi, K. Seto, J. Moss, and M. Noda.
    • Organizer
      Bethesda, USA
    • Place of Presentation
      Bethesda, USA
    • Year and Date
      2016-01-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Shiga-toxigenic Escherichia coli produced SubAB enters via lipid-raft- and an actin-dependent endocytosis in HeLa cells.2015

    • Author(s)
      八尋錦之助、永澤明佳,齋藤久子 ,岩瀬博太郎,野田公俊
    • Organizer
      49th U.S.-Japan Conference on Cholera and Other Enteric Bacterial Infections
    • Place of Presentation
      フロリダ(米国)
    • Year and Date
      2015-01-14 – 2015-01-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 腸管出血性大腸菌の産生するSubtilase cytotoxin の細胞侵入機構の解析2014

    • Author(s)
      永澤明佳,八尋錦之助,齋藤久子 ,岩瀬博太郎,野田公俊
    • Organizer
      第 97 回日本細菌学会関東支部総会
    • Place of Presentation
      東京ドームホテル(東京都・文京区)
    • Year and Date
      2014-10-30 – 2014-10-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] 腸管出血性大腸菌の産生するSubAB の細胞障害機構の解明2014

    • Author(s)
      八尋 錦之助、野田 公俊
    • Organizer
      第61回トキシンシンポジウム
    • Place of Presentation
      ルネッサンスリゾートナルト(徳島県・鳴門市)
    • Year and Date
      2014-09-03 – 2014-09-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 腸管出血性大腸菌の産生するSubtilase cytotoxin (SubAB)は アクチン及び脂質ラフト依存的に細胞内に取り込まれる」(若手奨励賞受賞)2014

    • Author(s)
      永澤明佳、小倉康平、津木博康、岩瀬博太郎、野田公俊、八尋錦之助
    • Organizer
      第61回トキシンシンポジウム
    • Place of Presentation
      ルネッサンスリゾートナルト(徳島県・鳴門市)
    • Year and Date
      2014-09-03 – 2014-09-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Inhibition of autophagy by SubAB is regulated by PERK-dependent pathway in Hela cells2014

    • Author(s)
      Kinnosuke Yahiro, Masatoshi Noda
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Characterization of Shiga-toxigenic Escherichia coli Sub AB uptake pathway in HeLa cells2014

    • Author(s)
      Sayaka Nagasawa, Kinnosuke Yahiro, Kohei Ogura, Hiroyasu Tsutsuki, Masatoshi Noda
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 一酸化窒素還元酵素:腸管出血性大腸菌の志賀毒素産生に影響を与える新規病原因子2014

    • Author(s)
      Takeshi Shimizu
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] The surface sensor NlpE of enterohemorrhagic Escherichia coli contributes to2014

    • Author(s)
      Takeshi Shimizu, Kimitoshi Ichimura and Masatoshi Noda
    • Organizer
      48th US-Japan Cooperative Medical Sciences Program Conference on Cholera and Other Bacterial Enteric Infections
    • Place of Presentation
      Dhaka, Bangladesh
    • Related Report
      2013 Annual Research Report
  • [Presentation] 腸管出血性大腸菌の産生するSubAB の PERKを介したアポトーシス制御機構2013

    • Author(s)
      Kinnnosuke Yahiro, Hiroyasu Tsutsuki, Masatoshi Noda
    • Organizer
      第60回毒素シンポジウム
    • Place of Presentation
      兵庫県
    • Related Report
      2013 Annual Research Report
  • [Presentation] Subtilase cytotoxin induces stress granule formation through PERK dependent pathway2013

    • Author(s)
      Hiroyasu Tsutsuki, Kinnosuke Yahiro, Tohru Shimizu, Masatoshi Noda
    • Organizer
      第86回日本細菌学会総会
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Helicobacter pylori VacA-induced autophagy and apoptosis are regulated by LRP1.2013

    • Author(s)
      Kinnosuke Yahiro, Masayuki Nakano, Masatoshi Noda, Toshiya Hirayama
    • Organizer
      第86回日本細菌学会総会
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Role for the surface senssor NlpE of enterohemorrhagic Escherichia coli in adherence to cells.2013

    • Author(s)
      Takeshi Shimizu, Masatoshi Noda
    • Organizer
      第86回日本細菌学会総会
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Shiga toxin and a novel toxin produced by Shiga-toxigenic Escherichia coli.2012

    • Author(s)
      Masatoshi Noda
    • Organizer
      The 11^<th> Korea-Japan International Symposium on Microbiology
    • Place of Presentation
      韓国
    • Year and Date
      2012-09-14
    • Related Report
      2012 Annual Research Report
  • [Presentation] Characterization of V cholerae Cholix-induced cell death mechanism in human cell line2012

    • Author(s)
      Kinnosuke Yahiro
    • Organizer
      The 11^<th> Korea-Japan International Symposium on Microbiology
    • Place of Presentation
      韓国
    • Year and Date
      2012-09-14
    • Related Report
      2012 Annual Research Report
  • [Presentation] Inhibitory effect of subtilase cytotoxin on LPS-induced nitric oxide production by macrophages.2012

    • Author(s)
      Hiroyasu Tsutsuki, Kinnosuke Yahiro, Takeshi Shimizu and Masatoshi Noda
    • Organizer
      THE 33rd NAITO CONFERENCE ON Oxygen Biology : Hypoxia, Oxidative Stress and Diseases.
    • Place of Presentation
      シャトレーゼガトーキングダム札幌(北海道)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 腸管出血性大腸菌の産生するSubABのPERKを介したアポトーシス制御機構2012

    • Author(s)
      八尋 錦之助、津々木 博康、小倉康平、野田 公俊
    • Organizer
      第59回トキシンシンポジウム
    • Place of Presentation
      とかちプラザ(北海道)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 腸管出血性大腸菌の産生する志賀毒素以外の毒素2012

    • Author(s)
      八尋錦之助、津々木博康、小倉康平、野田公俊
    • Organizer
      第95回日本細菌学会関東支部総会
    • Place of Presentation
      ホテル日航東京(東京)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Inhibitory effect of SubAB cytotoxin of enterohemorrhagic Escherichia coli on LPS-induced nitric oxide production by macrophages2012

    • Author(s)
      Hiroyasu Tsutsuki and Masatoshi Noda
    • Organizer
      2012 IEIIS in National Center of Sciences Building
    • Place of Presentation
      国立情報学研究所(東京)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Regulation of Subtilase cytotoxin (SubAB)-induced cell death by a PKR-like endoplasmic reticulum kinase (PERK)-dependent proteasome pathway in HeLa cells2012

    • Author(s)
      Kinnosuke Yahiro, Hiroyasu Tsutsuki, Kohei Ogura, Sayaka Nagasawa, Takeshi Shimizu, Joel Moss, Masatoshi Noda
    • Organizer
      7th US-Japan Cholera and Other Bacterial Enteric Infections Joint Panel Meeting.
    • Place of Presentation
      千葉大学薬学部創立120周年記念講堂(千葉)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Subtilase cytotoxin enhances E. coli survival in macrophages by suppression of nitric oxide production through the inhibition of NF-kB activation.2012

    • Author(s)
      Hiroyasu Tsutsuki, Kinnosuke Yahiro, Takeshi Shimizu, Masatoshi Noda
    • Organizer
      47th US Japan Cholera and Other Bacterial Enteric Infections Joint Panel Meeting.
    • Place of Presentation
      千葉大学薬学部創立120周年記念講堂(千葉)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 病原細菌のAB5型トキシンの作用機構等に関する研究

    • Author(s)
      Masatoshi Noda
    • Organizer
      第23回学会賞受賞者特別講演会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] Handbook of Proteolytic Enzymes, 3^<rd> Edition [Cytotoxin SubAB (Chapter 694)]2013

    • Author(s)
      Yahiro, K., J. Moss, and M. Noda
    • Publisher
      Elsevier
    • Related Report
      2012 Annual Research Report

URL: 

Published: 2012-04-24   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi