Screening of drug discovery seed compounds for recurrent C. difficile infection

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08514
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Kitasato University
• Principal Investigator: Matsui Hidehito 北里大学, 感染制御科学府, 講師 (80503797)
• Co-Investigator(Kenkyū-buntansha): 内山 淳平 岡山大学, 医歯薬学域, 准教授 (20574619)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Clostridioides difficile / CDI / Binary toxin / 毒素 / 芽胞

Outline of Final Research Achievements

Recurrence of C. difficile infection is a serious problem in clinical settings. In this study, we aimed to identify the seed compound of drug development for CDI. ELISA system for Toxin B and binary toxin were established, and a library of natural compounds was evaluated using the screening method for inhibitory activity to bacterial growth, spore formation, or toxin production. From the screening results, the compounds with inhibitory activity for bacterial growth, spore formation, and toxin production were shown in 19, 10, and 7 compounds, respectively. These hit compounds indicated the antibacterial activity superior to existing antimicrobial agents or specific inhibitory activity for toxin production or spore formation, therefore these compounds are expected for further evaluation in the future.

Free Research Field

化学療法学

Academic Significance and Societal Importance of the Research Achievements

C. difficile感染症(CDI)は、従来の抗菌薬治療において、10～30%の症例において再発が起こり、再発例ではさらなる再発を繰り返すリスクが高まり難治化することが報告されている。本研究で見出した天然化合物は新たなCDI治療薬の創製に向けたシード化合物になる可能性があることや、その作用機構の解析は、新たな薬剤開発の標的の同定に繋がることからが学術的および社会的意義は大きいと考える。