Analysis of the intracellular signal transduction pathways involved in the virulence of dermatophytes.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15438
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Musashino University
• Principal Investigator: Ishii Masaki 武蔵野大学, 薬学部, 助教 (10786966)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 皮膚糸状菌 / 細胞内シグナル伝達 / 感染 / 抗真菌薬 / 薬剤標的 / 遺伝子組み換え / Gタンパク質 / プロテインキナーゼ

Outline of Final Research Achievements

Tinea pedis (athlete's foot) is a fungal infection caused by dermatophytes and is so common that one out of five Japanese people have tinea pedis. In this project, I focused on the Rac and CDC42 pathways, which are necessary for the mycelial growth of dermatophytes, and analyzed the function of p21-activated kinase (PAK), a protein kinase that works downstream of the Rac pathway. I found that deletion of Cla4, one of the PAKs in dermatophytes, resulted in abnormal mycelial growth and localization of the cytoskeletal protein actin. Furthermore, in an invertebrate model of dermatophyte infection, inhibitors of Cla4 prolonged animal survival. These findings suggest that Cla4 may be a new target for antifungal drugs.

Free Research Field

微生物学

Academic Significance and Societal Importance of the Research Achievements

世界的な高齢化に伴い白癬の罹患者数も増加傾向にあります。白癬治療薬の作用標的は非常に限られており、近年報告が増加している薬剤耐性真菌の出現などにより危惧される難治性の白癬を治療するためにも、新規作用標的を持つ抗真菌薬の開発が望まれています。本課題では、Cdc24-Cdc42/Rac-Cla4経路はアクチンを介して皮膚糸状菌の菌糸成長を制御し、爪などの組織における生育においても重要な役割を果たすことを見出しました。このことから、本シグナル伝達経路が新たな抗真菌薬治療標的候補となることが期待されます。