Search for metallo-beta-lactamase inhibitors produced by microorganisms

• Project/Area Number: 26450142
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bioorganic chemistry
• Research Institution: Kitasato 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: ¥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.

Research Products

• [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
  • 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
  • Invited
• [Presentation] New metallo-beta-lactamase inhibitor produced by Paecilomyces sp. FKI-6801 (2015)
  • 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
  • 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
• [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