Elucidating the Mechanisms of Drug Resistance in Multidrug-Resistant Filamentous Fungal Respiratory Infections Using Genome Editing Technology

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08834
• 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: National Institute of Infectious Diseases
• Principal Investigator: Umeyama Takashi 国立感染症研究所, 真菌部, 室長 (20360696)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 真菌症 / 糸状菌 / ゲノム編集 / ゲノム解析 / 薬剤耐性

Outline of Final Research Achievements

Genomic information was obtained from various species of drug-resistant filamentous fungi, establishing a foundation for elucidating resistance mechanisms. Using CRISPR/Cas9 genome editing technology, the direct involvement of the Cyp51A gene in azole resistance in Aspergillus lentulus was demonstrated. A foundational technique for introducing CRISPR/Cas9 into the multidrug-resistant fungus Lomentospora prolificans was established. A CRISPR plasmid library for A. fumigatus was created, a high-efficiency transformation method was developed, and verification of CRISPR screening was initiated. These findings provide crucial insights that could lead to the development of new treatments and early detection methods for drug resistance in invasive fungal infections.

Free Research Field

医真菌学

Academic Significance and Societal Importance of the Research Achievements

本研究は深在性真菌症、特に薬剤耐性糸状菌感染症の分子メカニズム解明に貢献した。CRISPR/Cas9技術を用いた遺伝子機能解析により、アゾール耐性機構の一端を明らかにし、早期耐性検出法や新規治療法開発の基盤を構築した。また、多様な真菌種に応用可能なゲノム編集技術を確立し、真菌学研究の発展に寄与した。これらの成果は、致死率の高い深在性真菌症の診断・治療改善につながり、患者の予後向上に貢献する可能性がある。環境中の耐性株問題にも示唆を与え、ワンヘルスアプローチによる対策に重要な知見をもたらした。本研究で確立された技術は、他の病原真菌研究にも応用可能で、幅広い真菌感染症対策への波及効果が期待される。