Development of lead commands for new anti-infective agents

• Project/Area Number: 26670043
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Natural medicines
• Research Institution: The University of Tokyo
• Principal Investigator: HAMAMOTO Hiroshi 東京大学, 薬学研究科(研究院), 助教 (90361609)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 抗菌薬 / 化合物ライブラリー / カイコ / 作用機序解析 / 感染症

Outline of Final Research Achievements

We evaluated antimicrobial activity and mechanistic analysis of the compounds which identified by therapeutic effectiveness on silkworm infection model. These compounds showed antimicrobial activity against Staphylococci, and one of compound showed prolonged proliferation activity on mouse systemic infection model. This compound is implied to have a novel mechanism. These results suggest that silkworm infection model is useful model to identity therapeutically effective antimicrobial compounds from synthetic compounds library.

Research Products

• [Journal Article] Identification of lysocin E using a silkworm model of bacterial infection (2016)
  • Author(s): Hamamoto, H. Sekimizu, K.
  • Journal Title: Drug Discoveries & Therapeutics Volume: 10 Issue: 1 Pages: 24-29
  • DOI: 10.5582/ddt.2016.01012
  • NAID: 130005133325
  • ISSN: 1881-7831, 1881-784X
  • Open Access / Acknowledgement Compliant
• [Journal Article] Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis (2015)
  • Author(s): Ishii K, Tabuchi F, Matsuo M, Tatsuno K, Sato T, Okazaki M, Hamamoto H, Matsumoto Y, Kaito C, Aoyagi T, Hiramatsu K, Kaku M, Moriya K, Sekimizu K.
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 17092-17092
  • DOI: 10.1038/srep17092
  • Peer Reviewed / Open Access
• [Journal Article] 新規MRSA抗生物質ライソシンEの発見 -カイコを用いる治療効果を指向したスクリーニング創薬 (2015)
  • Author(s): 浜本洋、関水和久
  • Journal Title: 化学 Volume: 70 Pages: 12-16
  • NAID: 40020505825
• [Journal Article] Rational design, synthesis, and biological evaluation of lactam-bridged gramicidin a analogues: Discovery of a low-hemolytic antibacterial peptide (2015)
  • Author(s): J. Mao, T. Kuranaga, H. Hamamoto, K. Sekimizu, M. Inoue
  • Journal Title: ChemMedChem Volume: 10 Issue: 3 Pages: 540
  • DOI: 10.1002/cmdc.201402473
  • Peer Reviewed
• [Journal Article] カイコをモデル動物とした創薬研究展開 (2014)
  • Author(s): 浜本洋
  • Journal Title: JATAFFジャーナル Volume: 2 Pages: 38-43
• [Journal Article] カイコを用いた創薬研究 (2014)
  • Author(s): 松本靖彦、浜本洋、西田智、関水和久
  • Journal Title: 生体の科学 Volume: 65 Pages: 613-620
  • NAID: 40020290149
• [Journal Article] カイコをモデル動物とした創薬 (2014)
  • Author(s): 浜本洋、関水和久
  • Journal Title: 生化学 Volume: 85 Pages: 578-582
• [Presentation] カイコ感染実験系の有用性と課題 ライソシンEの研究を中心として (2016)
  • Author(s): 浜本洋
  • Organizer: メディカル・サイエンス セミナー
  • Place of Presentation: 学士会館（千代田区神保町）
  • Year and Date: 2016-03-24
  • Invited
• [Presentation] Identification and mechanistic analysis of a novel antibiotic lysocin E (2016)
  • Author(s): Hiroshi Hamamoto, Kazuhisa Sekimizu
  • Organizer: The 8th Japan-Korea Chemical Biology Symposium
  • Place of Presentation: Pacific Hotel Okinawa (Okinawa, Japan)
  • Year and Date: 2016-01-18
  • Invited
• [Presentation] カイコ細菌感染モデルにて同定された新規抗生物質ライソシンE (2015)
  • Author(s): 浜本洋、関水和久
  • Organizer: 第64回日本感染症学会東日本地方学術集会、第62回日本化学療法学会東日本支部総会 合同学会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
  • Year and Date: 2015-10-21
  • Invited
• [Presentation] カイコ真菌感染モデルを利用した抗真菌薬の治療効果の評価と探索 (2015)
  • Author(s): 浜本洋、関水和久
  • Organizer: 第36回関東医真菌懇話会
  • Place of Presentation: 京王プラザホテル（新宿区西新宿）
  • Year and Date: 2015-06-27
• [Presentation] カイコモデルを用いた治療効果を有する新規抗菌薬の同定と開発 (2015)
  • Author(s): 浜本洋、石井健一、安川淳一朗、西田智、関水和久
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸学園大学（兵庫県神戸市）
  • Year and Date: 2015-03-26 – 2015-03-28
  • Invited
• [Presentation] The primary sigma factor of bacterial RNA polymerase is involved in antimicrobial activity of a novel therapeutically effective antimicrobial agent. (2014)
  • Author(s): Paudel Atmika, Hamamoto Hiroshi, Kaneko Keichi, Matsunaga Shigeki, Suzuki Yutaka, Kanai Motomu, Kazuhisa Sekimizu.
  • Organizer: The 3rd International Symposium on Chemical Biology of Natural Products: Target ID and Regulation of Bioactivity
  • Place of Presentation: 千里ライフサイエンスセンター（大阪府豊中市）
  • Year and Date: 2014-10-28 – 2014-10-29
• [Presentation] Novel Therapeutically Effective Antimicrobial Agent Targets Bacterial RNA Polymerase Sigma Factor A (2014)
  • Author(s): Paudel Atmika, Hamamoto Hiroshi, Kaneko Keichi, Matsunaga Shigeki, Suzuki Yutaka, Kanai Motomu, Kazuhisa Sekimizu
  • Organizer: The 54th Interscience Conference on Antimicrobial Agents and Chemotherapy
  • Place of Presentation: Washington（USA）
  • Year and Date: 2014-09-05 – 2014-09-09
• [Presentation] Silkworm as an animal model for novel antibiotic development (2014)
  • Author(s): Hiroshi Hamamoto, Jyunichiro Yasukawa, Kenich Ishii, Atmika Paudel, Kazuhisa Sekimizu
  • Organizer: the Xth European Congress of Entomology
  • Place of Presentation: York（England）
  • Year and Date: 2014-08-03 – 2014-08-05
  • Invited
• [Remarks] 微生物薬品化学教室のホームページ
  • URL: http://www.f.u-tokyo.ac.jp/~bisei/index.html
• [Remarks] 東京大学大学院薬学系研究科微生物薬品化学のホームページ
  • URL: http://www.f.u-tokyo.ac.jp/~bisei/index.html