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Role of stringent response in survival, colonization and expression of pathogenesis in Helicobacter pylori

Research Project

Project/Area Number 16K08787
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionKyorin University

Principal Investigator

Kamiya Shigeru  杏林大学, 保健学部, 教授 (10177587)

Co-Investigator(Kenkyū-buntansha) 花輪 智子  杏林大学, 医学部, 准教授 (80255405)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsピロリ菌 / 緊縮応答 / バイオフィルム / 病原性 / 鞭毛 / 遺伝子発現 / 発現 / 定着 / ppGpp / spoT / 運動能 / ストレス感受性 / 臨床分離株 / 過酸化物感受性 / 変異株 / Hlicobacter pylori / 緊急応答 / 持続感染
Outline of Final Research Achievements

Stringent response is a bacterial response to adapt nutrient deprivation environment. When bacteria starve, guanosine pentaphosphate and guanosine tetraphosphate (collectively named (p)ppGpp) are accumulated in the cell and start to modulate gene expressions. Thereby, various physiological changes such as tolerance to stresses, induction of second metabolites and expression of virulence factors are occurred.
Infection of Helicobacter pylori causes gastritis and increases a risk of gastric cancer In the present study, we investigated the role of (p)ppGpp in H. pylori using a mutant lacking (p)ppGpp production. Accordingly, (p)ppGpp was shown to be important for formation of biofilm in addition to adaptation under oxidative and acidic stress environments. Furthermore, (p)ppGpp related to motility and formation of flagella. Taken together, (p)ppGpp is suggested to regulate biofilm formation via flagella formation.

Academic Significance and Societal Importance of the Research Achievements

ピロリ菌は慢性感染することで胃がんの発生要因となる。従って、除菌治療を行うことは重要であり、現在ピロリ菌感染者には抗菌薬の投与が行われている。一方で、耐性菌は増加しており、今後さらに治療が困難となることが考えられる。
本菌の定着には多くの因子が関与しているが、本課題により(p)ppGppが鞭毛形成を介してバイオフィルム形成に関与していることが示唆された。今後、(p)ppGppアナログや合成酵素阻害剤の開発により、これまでの抗菌薬と異なる治療法の開発につながるものと期待している。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(19 results)

All 2020 2019 2018 2017 2016

All Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Book (2 results)

  • [Journal Article] Serum Pepsinogen Values in Japanese Junior High School Students With Reference to <i>Helicobacter Pylori</i> Infection2020

    • Author(s)
      Okuda M, Lin Y, Mabe K, Kato M, Osaki T, Miyamoto R, Okumura A, Kamiya S, Kikuchi S.
    • Journal Title

      Journal of Epidemiology

      Volume: 印刷中 Issue: 1 Pages: 30-36

    • DOI

      10.2188/jea.je20180119

      10.2188/jea.JE20180119

    • NAID

      130007782484

    • ISSN
      0917-5040, 1349-9092
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Helicobacter pylori biofilm formation on susceptibility to amoxicillin, metronidazole and clarithromycin.2019

    • Author(s)
      Yonezawa H, Osaki T, Hojo F, Kamiya S
    • Journal Title

      Microbial Pathogenesis

      Volume: 132 Pages: 100-108

    • DOI

      10.1016/j.micpath.2019.04.030

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of probiotics in eradication therapy for Helicobacter pylori infection.2019

    • Author(s)
      Kamiya S, Yonezawa H, Osaki T
    • Journal Title

      Advances in Experimental Medicine and Biology

      Volume: - Pages: 243-255

    • DOI

      10.1007/5584_2019_369

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced infectivity of strains of Helicobacter pylori isolated from children compared with parental strains2019

    • Author(s)
      Zaman Cynthia、Osaki Takako、Furuta Yoshikazu、Hojo Fuhito、Yonezawa Hideo、Konno Mutsuko、Kurata Satoshi、Hanawa Tomoko、Kamiya Shigeru
    • Journal Title

      J Med Microbiol.

      Volume: 68 Pages: 633-641

    • DOI

      10.1099/jmm.0.000918

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influence of Intestinal Indigenous Microbiota on Intrafamilial Infection by Helicobacter pylori in Japan.2019

    • Author(s)
      Osaki T, Zaman C, Yonezawa H, Lin Y, Okuda M, Nozaki E, Hojo F, Kurata S, Hanawa T, Kikuchi S, Kamiya S.
    • Journal Title

      日本ヘリコバクター学会誌

      Volume: 9 Pages: 117-122

    • DOI

      10.3389/fimmu.2018.00287

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CYP3A4/5 genotype status and outcome of vonoprazan-containing Helicobacter pylori eradication therapy in Japan2017

    • Author(s)
      Sugimoto M, Ban H, Hira D, Kamiya T, Otsuka T, Inatomi O, Bamba S, Terada T, Andoh A.
    • Journal Title

      Aliment, Pharmacol, Ther

      Volume: 45 Pages: 1009-1010

    • DOI

      10.1111/apt.13959

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Usefulness of detection of clarithromycin-resistant Helicobacter pylori from fecal specimens for young adults treated with eradication therapy2017

    • Author(s)
      Osaki Takako、Mabe Katsuhiro、Zaman Cynthia、Yonezawa Hideo、Okuda Masumi、Amagai Kenji、Fujieda Shinji、Goto Mitsuhide、Shibata Wataru、Kato Mototsugu、Kamiya Shigeru
    • Journal Title

      Helicobacter

      Volume: 22

    • DOI

      10.1111/hel.12396

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Helicobacter pylori sabA gene is associated with iron deficiency anemia in childhood and adolescence2017

    • Author(s)
      Kato Seiichi、Osaki Takako、Kamiya Shigeru、Zhang Xue-Song、Blaser Martin J.
    • Journal Title

      PLOS ONE

      Volume: 12

    • DOI

      10.1371/journal.pone.0184046

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diversification of the AlpB Outer Membrane Protein of Helicobacter pylori Affects Biofilm Formation and Cellular Adhesion2017

    • Author(s)
      Hideo Yonezawa, Takako Osaki, Toshiyuki Fukutomi, Tomoko Hanawa, Satoshi Kurat, Cynthia Zaman, Fuhito Hojo, Shigeru Kamiya
    • Journal Title

      J Bacteriol.

      Volume: 199 Pages: 199-199

    • DOI

      10.1128/jb.00729-16

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Nation-wide survey of Helicobacter pylori treatment for children and adolescents in Japan.2017

    • Author(s)
      Okuda M, Kikuchi S, Mabe K, Osaki T, Kamiya S, Fukuda Y, Kato M
    • Journal Title

      Pediatrics International

      Volume: 59 Pages: 57-61

    • DOI

      10.1111/ped.13038

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Safety assessment of the Clostridium butyricum MIYAIRI 588 probiotic strain including evaluation of antimicrobial sensitivity and presence of Clostridium toxin genes in vitro and teratogenicity in vivo.2016

    • Author(s)
      Isa K, Oka K, Beauchamp N, Sato M, Wada K, Ohtani K, Nakanishi S, McCartney E, Tanaka M, Shimizu T, Kamiya S, Kruger C, Takahashi M
    • Journal Title

      Hum Exp Toxicol.

      Volume: 35 Pages: 818-832

    • DOI

      10.1177/0960327115607372

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] ピロリ菌のバイオフィルム形成に対するppGpp欠損の影響2018

    • Author(s)
      宮岡千尋,花輪智子,川上速人,河野洋平,青山隆夫,神谷茂
    • Organizer
      日本薬学会第138年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ピロリ菌における緊縮応答の役割2018

    • Author(s)
      宮岡千尋、花輪智子、青山隆夫、川上速人、神谷茂
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] Involvement of stringent response in oxidative stress response and biofilm formation in Helicobacter pylori infection2017

    • Author(s)
      Kamiya S, Yonezawa H, Hojo F, Osaki T, Hanawa T
    • Organizer
      XXXth International Workshop on Helicobacter & Microbiota in Inflammation & Cancer
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Involvement of stringent response in oxidative stress response and biofilm formation in Helicobacter pylori infection2017

    • Author(s)
      Kamiya S, Yonezawa H, Hojo F, Osaki T, Hanawa T
    • Organizer
      The 30th International Congress of Chemotherapy and Infection
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comparison of infectivity of H. pylori strains isolated from father, mother and 3 children of a family in gerbil model.2016

    • Author(s)
      Kamiya S, Zaman C, Yonezawa H, Hojo F, Osaki T
    • Organizer
      The 14th Internatiional Workshop on Helicobacter & Microbiota in Inflammation and Cancer.
    • Place of Presentation
      Magdeburg, Germany
    • Year and Date
      2016-09-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Intrafamiliar infection of Helicobacter pylori2016

    • Author(s)
      Kamiya, S
    • Organizer
      The 2nd International Conference on Mongolian Medicine Industry Expo and the Eurasia-Pacific University Alliance of Mongolian Medicine Academic Forum
    • Place of Presentation
      Tongliao, China
    • Year and Date
      2016-08-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] 腸内細菌叢と腸管免疫、高齢者感染症~超高齢社会の課題と特徴2016

    • Author(s)
      神谷 茂
    • Total Pages
      223
    • Publisher
      医薬ジャーナル社
    • Related Report
      2016 Research-status Report
  • [Book] 腸内フローラシンポジウム242016

    • Author(s)
      神谷 茂(編集)
    • Total Pages
      83
    • Publisher
      医薬出版
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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