| Project/Area Number |
18K07087
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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 | Saga University |
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Principal Investigator |
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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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 赤痢アメーバ / シスト形成 / 含硫脂質代謝 / コレステロール硫酸 / 脂質組成 / 含硫脂質 / 輸送体 |
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| Outline of Final Research Achievements |
Entamoeba histolytica, a protozoan parasite, causes amoebiasis, which is a global public health problem. We previously showed that cholesteryl sulfate (CS) plays an important role in Entamoeba encystation, a cell differentiation process from proliferative trophozoite into dormant cyst (Mi-ichi et al, PNAS 2015).
In this project, we analyzed the cellular localization of CS and its precious role during Entamoeba encystation using in vitro cultures of Entamoeba invadens as a E. histolytica model. Results showed that CS induced and maintained encysting cells as spherical maturing cysts in a dose-dependent manner. CS-treatment also caused time- and dose-dependent development of membrane impermeability in encysting cells via induction of de novo synthesis of dihydroceramides containing very long N-acyl chains(Mi-ichi et al, mSphere 2021; Mi-ichi et al, mSphere, 2022). Hence, these results indicate that CS-mediated morphological and physiological changes is necessary to form mature cysts.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではコレステロール硫酸が赤痢アメーバのシスト形成において、細胞膜に直接作用して細胞の球形化を誘導し、シスト壁形成の完了に繋がること、細胞膜の透過性を低下させ、成熟シストが乾燥耐性を獲得することを見出した。シストは寄生原虫が次の宿主へと到達するための必須形態であり、その形成過程の分子機構の解明は「寄生適応」という観点から寄生虫学の中心命題の1つである。一方で、休眠化は宿主への感染メカニズムを解き明かすことに繋がる。以上のことから、本研究によって得られた成果は赤痢アメーバの寄生適応戦略を解明する基礎研究としての意義と社界的意義があると考えている。
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