Elucidation of intracellular parasitic mechanisms using host-derived TAG by Mycobacterium leprae and search for new therapeutic targets

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07012
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Teikyo University
• Principal Investigator: TANIGAWA KAZUNARI 帝京大学, 薬学部, 講師 (10443110)
• Co-Investigator(Kenkyū-buntansha): 鈴木 幸一 帝京大学, 医療技術学部, 教授 (20206478)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ハンセン病 / らい菌 / 脂質 / ミコール酸 / マクロファージ

Outline of Final Research Achievements

Triacylglycerol (TAG) accumulated in host cells is important for the survival of Mycobacterium leprae (M. leprae）, but how the bacterium utilizes it is unknown. In this study, we investigated the possibility that TAG is utilized for the cell wall lipid mycolic acid of M. leprae. In THP-1 cells infected with M. leprae, fatty acids, which are metabolites of TAG, increased, and mycolic acid was subsequently detected, but this disappeared after treatment with a mycolic acid synthesis inhibitor. In M. leprae infected cells containing BODIPY-labeled TAG, BODIPY fluorescence was observed in the bacterium. These results suggest that M. leprae has metabolic activity for TAG in infected cells and uses the metabolites to synthesize mycolic acid for the bacilli.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

本申請課題によって、らい菌の細胞内寄生や生存に必須である宿主細胞内脂質について、その利用経路の１つが明らかになった。今後は、ミコール酸合成の阻害薬であるイソニアジドや宿主由来脂質の蓄積を防ぐような脂質代謝改善薬がハンセン病の新たな治療戦略として応用できると考えられる。現在のハンセン病治療薬は薬価が高いため、既に市場にある薬で応用できれば、貧困な国に多いハンセン病の治療薬として社会的意義がある。