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Analysis of uptake of serum proteins by the malarial parasite Plasmodium falciparum

Research Project

Project/Area Number 16K08759
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Parasitology (including sanitary zoology)
Research InstitutionOsaka University

Principal Investigator

Tougan Takahiro  大阪大学, 微生物病研究所, 助教 (20379093)

Research Collaborator HORII Toshihiro  
EDULA Jyotheeswara Reddy  
TSUBOI Takafumi  
TAKASHIMA Eizo  
MORITA Masayuki  
KIM Yoon-Jeong  
NUNOMURA Kazuto  
LIN Bang-Zhong  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
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)
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
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.

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。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(28 results)

All 2019 2018 2017 2016 Other

All Journal Article (10 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (17 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Remarks (1 results)

  • [Journal Article] Application of the automated haematology analyzer XN-30 for discovery and development of anti-malarial drugs2019

    • Author(s)
      Tougan Takahiro、Toya Yuji、Uchihashi Kinya、Horii Toshihiro
    • Journal Title

      Malaria Journal

      Volume: 18 Pages: 8-8

    • DOI

      10.1186/s12936-019-2642-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Leucophyllinines A and B, bisindole alkaloids from Leuconotis eugeniifolia2019

    • Author(s)
      Tang Yiming、Nugroho Alfarius Eko、Hirasawa Yusuke、Tougan Takahiro、Horii Toshihiro、Hadi A. Hamid A.、Morita Hiroshi
    • Journal Title

      Journal of Natural Medicines

      Volume: - Pages: 533-540

    • DOI

      10.1007/s11418-019-01297-5

    • NAID

      40021912663

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Application of the automated haematology analyzer XN-30 in an experimental rodent model of malaria2018

    • Author(s)
      Tougan Takahiro、Suzuki Yuhgi、Izuka Munehisa、Aono Kei、Okazaki Tomonori、Toya Yuji、Uchihashi Kinya、Horii Toshihiro
    • Journal Title

      Malaria Journal

      Volume: 17 Pages: 165-165

    • DOI

      10.1186/s12936-018-2313-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adaptation of the Plasmodium falciparum FCB strain for in vitro and in vivo analysis in squirrel monkeys ( Saimiri sciureus )2018

    • Author(s)
      Tougan Takahiro、Arisue Nobuko、Itagaki Sawako、Katakai Yuko、Yasutomi Yasuhiro、Horii Toshihiro
    • Journal Title

      Parasitology International

      Volume: 67 Pages: 601-604

    • DOI

      10.1016/j.parint.2018.05.012

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular Camouflage of Plasmodium falciparum Merozoites by Binding of Host Vitronectin to P47 Fragment of SERA52018

    • Author(s)
      Tougan T, Edula JR, Takashima E, Morita M, Shinohara M, Shinohara A, Tsuboi T, Horii T.
    • Journal Title

      Scientific Reports

      Volume: 22 Pages: 5052-5052

    • DOI

      10.1038/s41598-018-23194-9

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An automated haematology analyzer XN-30 distinguishes developmental stages of falciparum malaria parasite cultured in vitro2018

    • Author(s)
      Tougan T, Suzuki Y, Itagaki S, Izuka M, Toya Y, Uchihashi K, Horii T.
    • Journal Title

      Malar J.

      Volume: 17 Pages: 59-59

    • DOI

      10.1186/s12936-018-2208-6

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of SPP inhibitors suppressing propagation of HCV and protozoa2017

    • Author(s)
      Hirano J, Okamoto T, Sugiyama Y, Suzuki T, Kusakabe S, Tokunaga M, Fukuhara T, Sasai M, Tougan T, Matsunaga Y, Yamashita K, Sakai Y, Yamamoto M, Horii T, Standley DM, Moriishi K, Moriya K, Koike K, Matsuura Y.
    • Journal Title

      PNAS

      Volume: 114

    • DOI

      10.1073/pnas.1712484114

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Draft Genome Sequence of Plasmodium gonderi, a Malaria Parasite of African Old World Monkeys2017

    • Author(s)
      Honma H, Kawai S, Motooka D, Nakamura S, Tougan T, Horii T, Arisue N.
    • Journal Title

      Genome Announcements

      Volume: 5

    • DOI

      10.1128/genomea.00612-17

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanistic and structual basis of bioengineered bovine Cathelicidin-5 with optimized therapeutic activity2017

    • Author(s)
      Bikash R. Sahoo, Kenta Maruyama, Jyotheeswara R. Edula, Takahiro Tougan, Yuxi Lin, Young-Ho Lee, Toshihiro Horii, and Toshimichi Fujiwara
    • Journal Title

      Sci Rep.

      Volume: 7:44781 Pages: 44781-44781

    • DOI

      10.1038/srep44781

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunogenicity and protection from malaria infection in BK-SE36 vaccinated volunteers in Uganda is not influenced by HLA-DRB1 alleles.2016

    • Author(s)
      Tougan T, Ito K, Palacpac NM, Egwang TG, Horii T.
    • Journal Title

      Parasitol Int.

      Volume: 65 Pages: 455-458

    • DOI

      10.1016/j.parint.2016.06.012

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Direct activation of antimalarial immunity by artificial exposure of phosphatidylserine on malaria parasite-infected red blood cells2019

    • Author(s)
      東岸任弘、Jyotheeswara Reddy Edula、堀井俊宏
    • Organizer
      第88回日本寄生虫学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Application of an automated hematology analyzer XN-30 for discovery and development of antimalarial drugs in vitro2018

    • Author(s)
      Takahiro Tougan, Yuji Toya, Kinya Uchihashi, Toshihiro Horii
    • Organizer
      1st Malaria World Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多項目自動血球分析装置(XN-30)のげっ歯類マラリアモデルへの応用2018

    • Author(s)
      東岸任弘、鈴木裕義、井塚宗久、青野圭、岡﨑智紀、鳥家雄二、内橋欣也、堀井俊宏
    • Organizer
      第86回日本寄生虫学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Application of antimalarial drugs for malaria biology2017

    • Author(s)
      Takahiro Tougan, Sawako Itagaki, Yuhgi Suzuki, Tomonori Okazaki, Kinya Uchihashi and Toshihiro Horii
    • Organizer
      Japan-Brazil Malaria Workshop 2017
    • Place of Presentation
      サンパウロ大学(サンパウロ・ブラジル)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Application of antimalarial drugs for malaria biology2017

    • Author(s)
      Takahiro Tougan, Sawako Itagaki, Yuhgi Suzuki, Tomonori Okazaki, Kinya Uchihashi and Toshihiro Horii
    • Organizer
      U.S.-Japan Cooperative Medical Sciences Program (USJCMSP), 19th International Conference on Emerging Infectious Diseases in the Pacific Rim, Parasitic Disease Panel
    • Place of Presentation
      Novotel Ambassador(ソウル・韓国)
    • Year and Date
      2017-02-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification and analysis of compounds that inhibit binding between serum protein and P47 domain of Plasmodium falciparum SERA52017

    • Author(s)
      Takahiro Tougan
    • Organizer
      平成28年度 微研研究業績発表会
    • Place of Presentation
      大阪大学・微生物病研究所・谷口記念ホール(大阪)
    • Year and Date
      2017-01-20
    • Related Report
      2016 Research-status Report
  • [Presentation] マラリア原虫の赤血球期における増殖機構の定量学的解析2017

    • Author(s)
      東岸任弘
    • Organizer
      定量生物学の会 第八回年会
    • Place of Presentation
      自然科学研究機構 岡崎カンファレンスセンター(愛知)
    • Year and Date
      2017-01-08
    • Related Report
      2016 Research-status Report
  • [Presentation] 多項目自動血球分析装置(XN-30)によるマラリア原虫の検出と抗マラリア薬研究への応用2017

    • Author(s)
      東岸任弘、板垣佐和子、鈴木裕義、岡﨑智紀、内橋欣也、堀井俊宏
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 多項目自動血球分析装置(XN-30)の抗マラリア薬研究への応用2017

    • Author(s)
      東岸任弘
    • Organizer
      第28回日本臨床寄生虫学会大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Elucidation of a role of P47 domain of P. falciparum SERA52017

    • Author(s)
      Takahiro Tougan, Koji Adachi, Kazuto Nunomura, Bang-Zhong Lin, Yoon-Jeong Kim, and Toshihiro Horii
    • Organizer
      第86回日本寄生虫学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 抗マラリア薬研究における全自動マラリア感染赤血球検出試作装置の応用2016

    • Author(s)
      東岸任弘、板垣佐和子、鈴木裕義、岡﨑智紀、内橋欣也、堀井俊宏
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] HTRF法によるマラリア原虫・ヒト間タンパク質相互作用を阻害する化合物のスクリーニング系の構築とその応用2016

    • Author(s)
      東岸任弘、安達浩司、布村一人、林邦忠、金允政、堀井俊宏
    • Organizer
      第7回スクリーニング学研究会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Application of antimalarial drugs for malaria biology2016

    • Author(s)
      Takahiro Tougan
    • Organizer
      第563回微研集談会
    • Place of Presentation
      大阪大学・微生物病研究所・谷口記念ホール(大阪)
    • Year and Date
      2016-11-22
    • Related Report
      2016 Research-status Report
  • [Presentation] 抗マラリア薬研究における全自動マラリア感染赤血球検出試作装置の応用2016

    • Author(s)
      東岸任弘、板垣佐和子、鈴木裕義、岡﨑智紀、内橋欣也、堀井俊宏
    • Organizer
      第57回日本熱帯医学会大会
    • Place of Presentation
      一橋大学・一橋講堂(東京)
    • Year and Date
      2016-11-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Uptake mechanism of host serum proteins by malaria parasite, Plasmodium falciparum2016

    • Author(s)
      Takahiro Tougan, Jyotheeswara Reddy Edula, and Toshihiro Horii
    • Organizer
      第5回感染症若手フォーラム
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫)
    • Year and Date
      2016-09-06
    • Related Report
      2016 Research-status Report
  • [Presentation] TR-FRETを利用したタンパク質-ペプチド間相互作用を阻害する化合物のスクリーニング系の確立とその応用2016

    • Author(s)
      東岸任弘
    • Organizer
      第8回創薬を支援する先進スクリーニング技術セミナー
    • Place of Presentation
      大阪大学 大学院医学系研究科(大阪)
    • Year and Date
      2016-07-13
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] TR-FRETを利用したタンパク質-ペプチド間相互作用を阻害する化合物のスクリーニング系の確立とその応用2016

    • Author(s)
      東岸任弘
    • Organizer
      第8回創薬を支援する先進スクリーニング技術セミナー
    • Place of Presentation
      神戸大学 大学院医学研究科(楠キャンパス)(兵庫)
    • Year and Date
      2016-07-12
    • Related Report
      2016 Research-status Report
    • Invited
  • [Remarks] 大阪大学微生物病研究所難治感染症対策研究センター分子原虫学分野

    • URL

      http://www.biken.osaka-u.ac.jp/lab/protozool/index.html

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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