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Adjuvant heavy-chain antibody drug for antibiotics

Research Project

Project/Area Number 26460173
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Environmental and hygienic pharmacy
Research InstitutionTeikyo Heisei University

Principal Investigator

ISHIDA Isao  帝京平成大学, 薬学部, 教授 (00415556)

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords耐性菌 / ポンプ / 抗菌薬 / 多剤耐性緑膿菌 / 薬剤排出ポンプ / コリスチン / 緑膿菌 / 一本鎖抗体 / 排出システム
Outline of Final Research Achievements

Heavy chain antibodies (4P94 and 4P41) which bind with the Loop1 and Loop2 of the OprM (consisting a multi-drug resistant pump) existing outside of the outer membrane, have been isolated by using the M13-phage display method, respectively. The mono, di and trimers of the Heavy chain antibodies were designed and produced in E. coli. Those antibodies were purified with Protein A, His-Trap and Endotoxin-Trap columns. When pseudomonas aeruginosa (drug sensitive PAO-1, multi-drug resistant nalB and NCGM2.S1) were treated with colistin together with those antibodies, MIC (minimum growth-inhibition concentration) of the colistin decreased to a half to one fourth of the MIC with colistin alone. The side effects for the colistin-treatment in the clinical setting were known to be kidney and neurological failures. Co-treatment of colistin with those antibodies is anticipated to reduce the side effects.

Academic Significance and Societal Importance of the Research Achievements

本研究は、多剤耐性菌の薬剤排出システムを抑制する一本鎖VHH抗体を補助薬に使って、病原細菌の耐性化によって使用できなくなっている抗生物質医薬品を有効な抗菌薬としてリバイバルさせようというもので、実現できれば我が国の保健医療政策に大きな経済効果を及ぼすと期待される。

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (11 results)

All 2018 2016 2015 2014 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (9 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Silica nanoparticle-induced toxicity in mouse lung and liver imaged by electron microscopy2015

    • Author(s)
      Isoda, K, Kondoh, M, Yoshioka, Y, Tsutumi, Y, Imazawa, T, Nishimura, T, Ishida, I and Yagi, K.
    • Journal Title

      Fundamental Toxicological Science

      Volume: 2 Pages: 19-23

    • NAID

      130005083355

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Dペプチドの抗緑膿菌作用2018

    • Author(s)
      大野まき、西川毅、良原栄策、切替輝雄、石田功
    • Organizer
      第62回日本薬学会関東支部大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] TRAIL-R1を標的とした新規3価VHHを分泌するビフィズス菌によるがん治療2016

    • Author(s)
      西川毅、平裕一郎、平郁子、斎藤浩美、磯田勝広、石田功
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 粒子径10nm銀ナノ粒子の安全性評価に関する検討2016

    • Author(s)
      小林尚樹、磯田勝広、長谷川知也、秋元義弘、平裕一郎、平郁子、石田功
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 遺伝子組換え嫌気性菌による固形がん治療の研究2015

    • Author(s)
      石田功、西川毅、平裕一郎、平郁子、安西偕二郎
    • Organizer
      第8回中野医学会
    • Place of Presentation
      中野区医師会館(東京都中野区)
    • Year and Date
      2015-10-25
    • Related Report
      2015 Research-status Report
  • [Presentation] 医薬品リバイバル技術による創薬イノベーション2015

    • Author(s)
      石田功
    • Organizer
      平成27年度前橋工科大学大学院セミナー
    • Place of Presentation
      前橋工科大学(群馬県前橋市)
    • Year and Date
      2015-10-07
    • Related Report
      2015 Research-status Report
  • [Presentation] 遺伝子組換え嫌気性菌による固形がん治療2015

    • Author(s)
      石田功
    • Organizer
      Biotech2015アカデミックフォーラム
    • Place of Presentation
      東京ビックサイト(東京都江東区)
    • Year and Date
      2015-05-13
    • Related Report
      2015 Research-status Report
  • [Presentation] 細胞死誘導抗体を分泌するビフィズス菌を利用したがん治療2015

    • Author(s)
      西川毅、平裕一郎、平郁子、斎藤浩美、磯田勝広、石田功
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸大学(兵庫県神戸市)
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 10年先を見据えたテーマ発掘のノウハウ2014

    • Author(s)
      石田功
    • Organizer
      技術情報協会セミナー
    • Place of Presentation
      技術情報協会(東京都品川区)
    • Year and Date
      2014-07-17
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 遺伝子組換え嫌気性菌による固形がん治療2014

    • Author(s)
      石田功
    • Organizer
      Biotech2014アカデミックフォーラム
    • Place of Presentation
      東京ビッグサイト(東京都江東区)
    • Year and Date
      2014-05-14 – 2014-05-16
    • Related Report
      2014 Research-status Report
  • [Remarks] 私立大学戦略的研究基盤形成支援事業

    • URL

      http://pharm.thu.ac.jp/research/grant.html

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2023-01-30  

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