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Search for metallo-beta-lactamase inhibitors produced by microorganisms

Research Project

Project/Area Number 26450142
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bioorganic chemistry
Research InstitutionKitasato University

Principal Investigator

Shiomi Kazuro  北里大学, 感染制御科学府, 教授 (40235502)

Co-Investigator(Renkei-kenkyūsha) ASAMI Yukihiro  北里大学, 大学院感染制御科学府, 助教 (70391844)
MATSUMOTO Atsuko  北里大学, 大学院感染制御科学府, 准教授 (20300759)
HANAKI Hideaki  北里大学, 大学院感染制御科学府, 教授 (60286747)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords抗生物質 / 薬剤耐性 / 天然物化学 / 微生物化学 / スクリーニング / 薬剤耐性菌 / メタロ-β-ラクタマーゼ / 薬剤耐性克服 / 酵素阻害物質 / グラム陰性病原細菌
Outline of Final Research Achievements

We screened more than 10,000 cultured broths of actinomycetes and fungi that showed metallo-beta-lactamase (MBL) inhibition activity using MBL-producing clinically isolated strains of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. The paper disc method with or without meropenem was used for the screening, and we selected samples that displayed larger inhibition zone in the presence of meropenem. Large-scale culture was carried out for the selected samples, and we isolated the MBL inhibitory compounds from cultured broths of a Penicillium strain and a Paecilomyces strain. Though the compounds were known ones, their MBL inhibition activity has not been reported. Both compounds inhibited IMP-1 type MBL at the IC50 values of 20 μg/ml.

Report

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

    (5 results)

All 2017 2016 2015

All Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Presentation] 微生物二次代謝産物と感染症2017

    • Author(s)
      塩見和朗
    • Organizer
      理研シンポジウム:次世代微生物化学ワークショップ
    • Place of Presentation
      理化学研究所(埼玉県和光市)
    • Year and Date
      2017-01-06
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 薬剤耐性克服作用を示す微生物代謝産物の探索2016

    • Author(s)
      塩見和朗
    • Organizer
      日本薬学会第136年会シンポジウム「創薬研究における天然物化学のミッションと新潮流」
    • 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
    • Invited
  • [Presentation] New metallo-beta-lactamase inhibitor produced by Paecilomyces sp. FKI-68012015

    • Author(s)
      K. Shiomi, Y. Kashima, T. Suga, Y. Asami, T. Ishii, M. Iwatsuki, K. Nonaka, H. Matsui, H. Hanaki, S. Omura
    • Organizer
      ICAAC/ICC 2015
    • Place of Presentation
      サンディエゴ(米国)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 微生物代謝産物からのmetallo-β-lactamase阻害剤の探索2015

    • Author(s)
      鹿島由衣、須賀拓弥、浅見行弘、岩月正人、野中健一、大村 智、塩見和朗
    • Organizer
      日本農芸化学会2015年度大会
    • Place of Presentation
      岡山大学津島キャンパス(岡山市北区)
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 新規メタロ-β-ラクタマーゼ阻害剤2015

    • Inventor(s)
      大村 智、塩見和朗、浅見行弘、野中健一、鹿島由衣、花木秀明
    • Industrial Property Rights Holder
      北里大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-061943
    • Filing Date
      2015-03-25
    • Related Report
      2014 Research-status Report

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

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