| Project/Area Number |
18K07092
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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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| Review Section |
Basic Section 49040:Parasitology-related
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| Research Institution | Iryo Sosei University |
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Principal Investigator |
Nara Takeshi 医療創生大学, 薬学部, 教授 (40276473)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | クルーズトリパノソーマ / シャーガス病 / シスト形成 / 休眠 / Trypanosoma cruzi / 慢性シャーガス病 / 休眠体 |
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| Outline of Final Research Achievements |
Trypanosoma cruzi is a parasitic protist and causes Chagas disease. Chronic phase is characteristic to Chagas disease, like tuberculosis and toxoplasmosis, of which the pathogens become a dormant form. Here we demonstrate “a cyst-like form” of T. cruzi induced by treatment with concanavalin A (ConA). In the presence of ConA, epimastigote, an insect stage of T. cruzi, became swollen by enlargement of vacuole, leading to the formation of cyst wall. Cellular organelles, like nuclei, mitochondria, and flagella, multiplied synchronously within the cyst wall and then newly formed, motile organisms budded inside the vacuolar cavity. The daughter parasites survived at least 2 weeks in this form and, notably, were infective to the mammalian cells. Metabolomic analysis showed accumulation of glycolytic intermediates, suggesting the arrest of energy metabolism. Our data suggest that dormancy T. cruzi may be associated with long-lasting persistence of the parasites in chronic Chagas disease.
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| Academic Significance and Societal Importance of the Research Achievements |
シャーガス病における慢性化の機序として、これまでに細胞内寄生型amastigoteの中には「分裂しない」原虫が出現し、これが薬剤耐性や長期生存の原因となっている可能性が示唆されている（DOI: https://doi.org/10.7554/eLife.34039.001, 2018）。本研究で見出された嚢子型では解糖中間代謝産物の蓄積が認められ、休眠に近い代謝活性状態にあると考えられる。本研究の成果は、シャーガス病の慢性化の新たな機序として原虫の休眠現象を強く示唆するものであり、その分子基盤を明らかにすることによって新たな創薬標的の創出が期待できる点で、大きな学術的・社会的意義をもつ。
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