Inhibitory mechanisms of sphingolipid metabolizing enzyme activity by Mycobacterium tuberculosis-derived ManLAM
| Project/Area Number |
17K10031
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Infectious disease medicine
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 結核菌 / 病原性抗酸菌 / リポアラビノマンナン / ManLAM / 自然免疫 / スフィンゴ脂質代謝 / 好中球 / 食胞成熟 / スフィンゴ脂質代謝酵素 / スフィンゴ脂質 / ラクトシルセラミド / マイクロドメイン / ヒト好中球 / 抗酸菌感染 / マンノースキャップ型リポアラビノマンナン / 脂質ドメイン |
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| Outline of Final Research Achievements |
Lipoarabinomannan (LAM) is glycolipid that abundantly present in the cell walls of all mycobacterial species, including Mycobacterium tuberculosis. In particular, M. tuberculosis are known to have ManLAM and inhibit phagosome maturation. However, the detailed molecular mechanism is not well understood. The principal investigator hypothesized that ManLAM directly inhibits sphingolipid metabolism associated with LacCer-enriched lipid rafts in mycobacteria-containing phagosomes, resulting in intracellular survival of pathogenic mycobacteria, such as M. tuberculosis. The principal investigator found that pathogenic mycobacteria use ManLAM to inhibit the production of bioactive lipids through LacCer-enriched lipid rafts-dependent sphingolipid metabolism, thereby preventing phagosome maturation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究を行ったことで、スフィンゴ脂質代謝酵素及び生理活性脂質が関与する食胞成熟機構の全容解明に近づいた。このような学術的意義だけでなく、本研究では病原性抗酸菌がManLAMを利用してどのようにヒト自然免疫担当細胞内のスフィンゴ脂質代謝へ影響を与え寄生するのかを詳らかにした。そのため本研究成果は、上記メカニズムを標的とした新規病原性抗酸感染症の治療薬や治療法の開発に結び付いており、極めて社会的意義が大きいものである。
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Report
(7 results)
Research Products
(39 results)
