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Whole-genome sequencing of clarithromycin resistant Helicobacter pylori characterizes unidentified variants of multidrug resistant efflux pump genes

Research Project

Project/Area Number 26460212
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionThe University of Tokushima (2016)
Kobe Pharmaceutical University (2014-2015)

Principal Investigator

TANAHASHI Toshihito  徳島大学, 大学院医歯薬学研究部(医学系), 学術研究員 (30380067)

Research Collaborator AZUMA Takeshi  神戸大学, 医学部, 教授
OKADA Rina  神戸大学, 医学部, 技術補佐員
TAGUCHI Yoshihiro  中央大学, 理工学部, 教授
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords全ゲノムシークエンシング / ヘリコバクターピロリ菌 / 薬剤耐性 / クラリスロマイシン / 全ゲノムシークエンス / クラリスロマシシン
Outline of Final Research Achievements

Clarithromycin (CLR) is the key drug in eradication therapy of Helicobacter pylori (H. pylori) infection, and widespread use of CLR has led to an increase in primary CLR-resistant H. pylori. The known mechanism of CLR resistance has been established in A2146G and A2147G mutations in the 23S rRNA gene, but evidence of the involvement of other genetic mechanisms is lacking. Using the MiSeq platform, whole-genome sequencing of the 19 clinical strains and the reference strain ATCC26695 was performed. All sequencing reads of CLR-resistant strains had a G mutation in an identical position of the 23S rRNA gene. In addition, genetic variants of four gene clusters (hp0605-hp0607, hp0971-hp0969, hp1327-hp1329, and hp1489-hp1487) of TolC homologues, which have been implicated in multi-drug resistance, were examined. Gene clusters of TolC homologues are involved in CLR susceptibility profiles in individual H. pylori strains.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (10 results)

All 2017 2016 2015 2014

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Genetic variants of Helicobacter pylori type IV secretion system components CagL and CagI and their association with clinical outcomes2017

    • Author(s)
      Hirofumi Ogawa, Akira Iwamoto, Toshihito Tanahashi, Rina Okada, Koji Yamamoto, Shin Nishiumi, Masaru Yoshida, and Takeshi Azuma
    • Journal Title

      Gut Patohgens

      Volume: non Issue: 1 Pages: 9-21

    • DOI

      10.1186/s13099-017-0165-1

    • NAID

      120006557461

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Whole-genome sequencing of clarithromycin resistant Helicobacter pylori characterizes unidentified variants of multidrug resistant efflux pump genes.2014

    • Author(s)
      Iwamoto A, Tanahashi T, Okada R, Yoshida Y, Kikuchi K, Murakami Y, Yang L, Yamamoto K, Nishiumi S, Yoshida M, Azuma T.
    • Journal Title

      Gut Pathog

      Volume: - Issue: 1 Pages: 6-6

    • DOI

      10.1186/1757-4749-6-27

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ヘリコバクターピロリ菌のIV型分泌装置に関連するCagLとCagIの変異解析2016

    • Author(s)
      小川浩史、岩本彰、棚橋俊仁、山本幸字司、吉田優、東健.
    • Organizer
      第22回日本ヘリコバクター学会学術集会
    • Place of Presentation
      別府ビーコンプラザ(大分県、別府市)
    • Year and Date
      2016-06-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヘリコバクターピロリ菌IV型分泌装置を制御するCagLとCagIの変異解析2016

    • Author(s)
      小川浩史、岩本彰、棚橋俊仁、岡田理菜、張菁芸、吉田優、東健.
    • Organizer
      第102回日本消化器病学会総会
    • Place of Presentation
      京王プラザホテル(東京都、新宿区)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] 東アジアにおけるヘリコバクターピロリ菌癌性蛋白質CagAの解析2015

    • Author(s)
      岩本彰、棚橋俊仁、岡田理菜、小川浩史、張菁芸、吉田優、東健
    • Organizer
      NGS現場の会第四回研究会
    • Place of Presentation
      つくば国際会議場、茨城
    • Year and Date
      2015-07-03
    • Related Report
      2015 Research-status Report
  • [Presentation] 次世代シーケンサーを用いたヘリコバクターピロリ菌癌性蛋白CagAに特徴的な変異の検出2015

    • Author(s)
      岩本彰、棚橋俊仁、小川浩史、楊林、山本幸司、東健.
    • Organizer
      第21回日本ヘリコバクター学会学術集会
    • Place of Presentation
      神戸ポートピアホテル、神戸
    • Year and Date
      2015-06-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 6Whole-genome sequencing detects novel virulence variants of Helicobacter pylori cagA gene and its relationship with oncogenic CagA.2015

    • Author(s)
      Akira Iwamoto, Toshihito Tanahashi, Rina Okada, Hirofumi Ogawa, Chang Ching Yun, Masaru Yoshida, Takeshi Azuma.
    • Organizer
      DDW 2015
    • Place of Presentation
      Washington DC.
    • Year and Date
      2015-05-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 4次世代シーケンサーを用いたヘリコバクターピロリ菌癌性蛋白CagAに特徴的な変異の検出2015

    • Author(s)
      岩本彰、棚橋俊仁、岡田理菜、小川浩史、張菁芸、吉田優、東健
    • Organizer
      第9回日本ゲノム微生物学会年会
    • Place of Presentation
      神戸大学百年記念館、神戸
    • Year and Date
      2015-03-06 – 2015-03-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 5Detection of novel missense variants of Helicobacter pylori cagA gene using whole-genome sequencing2015

    • Author(s)
      Iwamoto Akira, Tanahashi Toshihito, Okada Rina, Hirofumi Ogawa, Chang Chingyun, Yoshida Masaru, Azuma Takeshi
    • Organizer
      第5回新学術発がんスパイラル国際シンポジウム
    • Place of Presentation
      神戸ポートピアホテル、神戸
    • Year and Date
      2015-02-26 – 2015-02-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 7次世代シークエンサーを用いた本邦におけるヘリコバクターピロリ菌cagA遺伝子の全ゲノム解析2014

    • Author(s)
      岩本彰、棚橋俊仁、楊林、山本幸司、東健
    • Organizer
      第20回日本ヘリコバクター学会学術集会
    • Place of Presentation
      東京ステーションコンファレンス、東京
    • Year and Date
      2014-06-28 – 2014-06-29
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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