| Project/Area Number |
16K08759
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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 |
Parasitology (including sanitary zoology)
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| Research Institution | Osaka University |
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Principal Investigator |
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| Research Collaborator |
HORII Toshihiro
EDULA Jyotheeswara Reddy
TSUBOI Takafumi
TAKASHIMA Eizo
MORITA Masayuki
KIM Yoon-Jeong
NUNOMURA Kazuto
LIN Bang-Zhong
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | マラリア原虫 / 感染赤血球 / 血清タンパク質 / 取り込み現象 / 血液凝固 / 播種性血液凝固症候群 / 取り込みメカニズム |
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| Outline of Final Research Achievements |
Malarial parasites require various host factors not only for their growth, but also for evading the host immune system. Previous studies regarding the utilization of host factors have focused mainly on ions and low-molecular weight compounds, such as lipids and vitamins. Therefore, less information is available on the utilization of host serum proteins. In the current study, we have comprehensively identified serum proteins taken up by parasites. Especially, three proteins, vitamin K-dependent protein S, prothrombin, and vitronectin, were selectively internalized in a Ca2+-dependent manner. Uptake of these proteins was initiated before DNA replication and increased during the trophozoite and schizont stages irrespective of the assembly/disassembly of actin filaments. In addition, it was demonstrated that prothrombin was cleaved and activated, causing blood coagulation. These findings indicated a mechanism of severe malarial complications such as disseminated intravascular coagulation.
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| Academic Significance and Societal Importance of the Research Achievements |
マラリアはエイズ、結核と並ぶ世界三大感染症の一つに数えられる熱帯感染症である。中でも熱帯熱マラリアは世界中で年間1億人以上が感染し、死亡数は50万人にのぼる。病原体であるマラリア原虫は蚊の吸血によって体内に侵入し、赤血球内で増殖する。マラリア原虫の宿主因子の利用については脂質、ビタミン類などの解析が先行しており、血清タンパク質の利用については十分な理解が得られていない。本研究では取り込まれる血清タンパク質を網羅的に同定し、その取り込みメカニズムを解析した。さらに病因との関係を解析し、マラリア症状の軽減、治療への応用への新たな手掛かりを得た。
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