Discovery of microorganism-derived anti-MRSA therapeutic seed compounds that inhibit drug resistance factors

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06616
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47050:Environmental and natural pharmaceutical resources-related
• Research Institution: Kitasato University
• Principal Investigator: Asami Yukihiro 北里大学, 感染制御科学府, 教授 (70391844)
• Co-Investigator(Kenkyū-buntansha): 君嶋 葵 北里大学, 感染制御科学府, 講師 (10832404)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 薬剤耐性因子

Outline of Final Research Achievements

The bacteria resistant to beta-lactam antibiotics are an increasing concern. Remarkably, Gram-positive bacteria, which resist beta-lactam antibiotics commonly express PBP2', a protein to which these antibiotics cannot bind, thus evading their antimicrobial effects. This represents the main mechanism of resistance. Tackling this issue, it is believed that the use of PBP2' inhibitors potentially restores the efficacy of beta-lactam antibiotics. We have re-discovered tetronomycin from microbial cultures as an active agent with potent antibacterial activity against MRSA and other major anti-Gram-positive bacteria from the past year. Furthermore, we discovered a novel derivative of tetronomycin and started to elucidate its structure-activity relationship with each other. We further isolated and structurally identified 11 compounds from filamentous fungal cultures that exhibit activity-enhancing effects of MEPM and discovered a novel compound, phomoidride H.

Free Research Field

微生物創薬

Academic Significance and Societal Importance of the Research Achievements

2050年にはAMRによる全世界での死亡者数が1,000万人以上になると予想されている。AMR対策に資する研究成果は、学術的意義や社会的意義が高いと考えられる。本研究課題はその問題解決の一つとして薬剤耐性因子を標的とした微生物創薬研究の基盤研究になると期待できる。今後も本研究課題を継続することで、新しい創薬シーズ化合物が取得できると期待している。