Mode of action study of tripropeptin C, which exhibits excellent in vivo efficacy superior to vancomycin

• Project/Area Number: 24710254
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Living organism molecular science
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: HASHIZUME Hideki 公益財団法人微生物化学研究会, 微生物化学研究所, 主任研究員 (10311276)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 薬剤耐性菌 / 院内感染 / トリプロペプチン / バンコマイシン / MRSA / トリプロペプチンC / 作用機序解析 / リポペプチド / 細胞壁合成 / 抗菌剤 / ペプチド系化合物

Research Abstract

Natural lipopeptide antibiotic tripropeptin C (TPPC) exhibits excellent in vivo efficacy in a mice-MRSA septicemia model. MRSA is well-known as multi-drug resistant, major nosocomial pathogen. The purpose of this study was to reveal how TPPC acts against MRSA. We found carboxylic acids in TPPC molecule are essential to exhibit antimicrobial activity. And we revealed the dissociation constant between TPPC and its target molecule UPP. We accomplished to produce isotope-labeled TPPC for the analysis of molecular based interaction by using solid-state NMR.

Research Products

• [Presentation] 新規抗MRSA抗生物質トリプロペプチンの作用機序解析- SPRを利用した低分子-低分子間相互作用解析の一例- (2013)
  • Author(s): 橋爪秀樹
  • Organizer: 第13回日本蛋白質科学会年会
  • Place of Presentation: とりぎん文化会館(鳥取市)
  • Year and Date: 2013-06-13
• [Presentation] 新規抗 MRSA 抗生物質トリプロペプチンの作用機序解析におけるSPR を利用した低分子ー低分子間相互作用解析 (2013)
  • Author(s): 橋爪秀樹
  • Organizer: 第13回 日本蛋白質科学会
  • Place of Presentation: とりぎん文化会館（鳥取）
  • Invited
• [Presentation] In Vitro Antimicrobial Activity and In Vivo Efficacy In a Mouse Staphylococcal-Septicemia Model of Water-soluble Tripropeptin C Analogs (2012)
  • Author(s): Sehei Hirosawa, Hideki Hashizume, Yoshihiko Kobayashi, Ryo Watabe, Kunio Inoue, Yuko Takahashi, Shigeko Harada, Syunichi Ohba, Tohru Masuda, Ryuichi Sawa, Yoshiaki Takahashi, Toshiaki Miyake, Akio Nomoto, Masakatsu Shibasaki
  • Organizer: 52^<nd> ICAAC
  • Place of Presentation: Moscone Convension Center (San Francisco, USA)
  • Year and Date: 2012-09-11
• [Presentation] In Vitro Antimicrobial Activity and In Vivo Efficacy In a Mouse Staphylococcal-Septicemia Model of Water-soluble Tripropeptin C Analogs (2012)
  • Author(s): S. Hirosawa, H. Hashizume, Y. Kobayashi, R. Watabe, K. Inoue, Y. Takahashi, S. Harada, S. Ohba*2, T. Masuda, R. Sawa, Y. Takahashi, T. Miyake, A. Nomoto and M. Shibasaki
  • Organizer: 52nd Interscience conference of antimicrobial agents and chemotherapy
  • Place of Presentation: Moscone Convension center, SanFrancisco, USA
• [Presentation] 新規抗MRSA抗生物質トリプロペプチンの作用機序解析 - SPR を利用した低分子-低分子間相互作用解析の一例 -
  • Author(s): 橋爪秀樹
  • Organizer: 第13回 日本蛋白質科学会
  • Place of Presentation: とりぎん文化会館（鳥取市）
• [Remarks]
  • URL: http://www.bikaken.or.jp/
• [Remarks] （公財）微生物化学研究会
  • URL: http://www.bikaken.or.jp/
• [Patent(Industrial Property Rights)] 併用抗メチシリン耐性黄色ブドウ球菌薬、及びβラクタム系抗生物質の抗菌活性増 強剤 (2013)
  • Inventor(s): 橋爪秀樹
  • Industrial Property Rights Holder: 公益財団法人 微生物化学研究会
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-249729
  • Filing Date: 2013-12-03
• [Patent(Industrial Property Rights)] 併用抗メチシリン耐性黄色ブドウ球菌薬、及びベータラクタム系抗生物質の抗菌活性増強剤 (2013)
  • Inventor(s): 橋爪秀樹
  • Industrial Property Rights Holder: （公財）微生物化学研究会
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013