Molecular mechanisms of erythrocyte invasion by malaria parasites

• Project/Area Number: 15K08448
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Nagasaki University
• Principal Investigator: YAHATA Kazuhide 長崎大学, 熱帯医学研究所, 助教 (40467965)
• Research Collaborator: KANEKO Osamu
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: マラリア / 赤血球侵入 / メロゾイト / マラリア原虫

Outline of Final Research Achievements

The pathology of malaria is caused by asexual stage parasite proliferation in erythrocytes. This amplification cycle involves merozoite release from infected erythrocytes followed by invasion of and growth within new erythrocytes. The essential steps of erythrocyte invasion are mediated by molecular mechanisms which are potential targets for the prevention and treatment of malaria. In this study, we generate conditional apical membrane antigen 1 (AMA1) knockout Plasmodium falciparum parasites and show that AMA1 is not involved in erythrocyte deformation immediately prior to erythrocyte internalisation, but is associated with the formation of the tight junction between the merozoite and the erythrocyte.

Academic Significance and Societal Importance of the Research Achievements

AMA1はマラリアワクチン候補抗原の一つであり、今回の成果によりマラリア原虫メロゾイトが赤血球に侵入する際にAMA1が赤血球侵入過程のどの場所で機能しているのかを詳細に明らかにすることが出来た。今後、AMA1-RON複合体を形成するRON2、RON4、RON5などの他の赤血球侵入分子の機能解析も進め、機能領域を明らかにすることで、新たなワクチン標的部位や複合体を阻害する薬剤の開発に貢献することが出来る。

Research Products

• [Int'l Joint Research] フランシス・クリック研究所(英国)
• [Journal Article] The Plasmodium knowlesi MAHRP2 ortholog localizes to structures connecting Sinton Mulligan's clefts in the infected erythrocyte (2018)
  • Author(s): Kumi Asare Kwame、Sakaguchi Miako、Byaruhanga Lucky Amuza、Asada Masahito、Miyazaki Shinya、Katakai Yuko、Kawai Satoru、Song Chihong、Murata Kazuyoshi、Yahata Kazuhide、Kaneko Osamu
  • Journal Title: Parasitology International Volume: 印刷中 Issue: 4 Pages: 481-492
  • DOI: 10.1016/j.parint.2018.04.005
  • Peer Reviewed / Open Access
• [Journal Article] Critical role of Erythrocyte Binding-Like protein of the rodent malaria parasite Plasmodium yoelii to establish an irreversible connection with the erythrocyte during invasion (2018)
  • Author(s): Kegawa Yuto、Asada Masahito、Ishizaki Takahiro、Yahata Kazuhide、Kaneko Osamu
  • Journal Title: Parasitology International Volume: 67 Issue: 6 Pages: 706-714
  • DOI: 10.1016/j.parint.2018.07.006
  • Peer Reviewed / Open Access
• [Journal Article] Fragment Molecular Orbital Study of the Interaction between Sarco/Endoplasmic Reticulum Ca2+-ATPase and its Inhibitor Thapsigargin toward Anti-Malarial Development (2018)
  • Author(s): Ishikawa Takeshi、Mizuta Satoshi、Kaneko Osamu、Yahata Kazuhide
  • Journal Title: The Journal of Physical Chemistry B Volume: 122 Issue: 33 Pages: 7970-7977
  • DOI: 10.1021/acs.jpcb.8b04509
  • Peer Reviewed / Open Access
• [Journal Article] Modulation of immune responses by Plasmodium falciparum infection in asymptomatic children living in the endemic region of Mbita, western Kenya (2018)
  • Author(s): Kijogi Caroline、Kimura Daisuke、Bao Lam Quoc、Nakamura Risa、Chadeka Evans Asena、Cheruiyot Ngetich Benard、Bahati Felix、Yahata Kazuhide、Kaneko Osamu、Njenga Sammy M.、Ichinose Yoshio、Hamano Shinjiro、Yui Katsuyuki
  • Journal Title: Parasitology International Volume: 67 Issue: 3 Pages: 284-293
  • DOI: 10.1016/j.parint.2018.01.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Plasmodium knowlesi MAHRP2 ortholog localizes to structures connecting Sinton Mulligan's clefts in the infected erythrocyte. (2018)
  • Author(s): Kumi Asare K, Sakaguchi M, Byaruhanga Lucky A, Asada M, Miyazaki S, Katakai Y, Kawai S, Song C, Murata K, Yahata K, Kaneko O
  • Journal Title: Parasitol International Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] マラリア原虫の赤血球侵入と放出の分子メカニズム (2018)
  • Author(s): 矢幡一英
  • Journal Title: 細胞 Volume: 49 Pages: 40-43
• [Journal Article] Rapid identification of genes controlling virulence and immunity in malaria parasites (2017)
  • Author(s): Abkallo HM, Martinelli A, Inoue M, Ramaprasad A, Xangsayarath P, Gitaka J, Tang J, Yahata K, Zoungrana A, Mitaka H, Acharjee A, Datta PP, Hunt P, Carter R, Kaneko O, Mustonen V, Illingworth CJR, Pain A, Culleton R
  • Journal Title: PLOS Pathogens Volume: 13 Issue: 7 Pages: e1006447-e1006447
  • DOI: 10.1371/journal.ppat.1006447
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Selections, frameshift mutations, and copy number variation detected on the surf 4.1 gene in the western Kenyan Plasmodium falciparum population. (2017)
  • Author(s): Gitaka JN, Takeda M, Kimura M, Idris ZM, Chan CW, Kongere J, Yahata K, Muregi FW, Ichinose Y, Kaneko A, Kaneko O
  • Journal Title: Malar Journal Volume: 16 Issue: 1 Pages: 98-109
  • DOI: 10.1186/s12936-017-1743-x
  • NAID: 120006987547
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Plasmodium knowlesi Skeleton-Binding Protein 1 Localizes to the 'Sinton and Mulligan' Stipplings in the Cytoplasm of Monkey and Human Erythrocytes (2016)
  • Author(s): Lucky AB, Sakaguchi M, Katakai Y, Kawai S, Yahata K, Templeton TJ, Kaneko O
  • Journal Title: PLOS ONE Volume: 11 Issue: 10 Pages: 0164272-0164272
  • DOI: 10.1371/journal.pone.0164272
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Plasmodium Rab5b is secreted to the cytoplasmic face of the tubovesicular network in infected red blood cells together with N-acylated adenylate kinase 2 (2016)
  • Author(s): Ebine K, Hirai M, Sakaguchi M, Yahata K, Kaneko O, Saito-Nakano Y.
  • Journal Title: Malar J. Volume: 15 Issue: 1 Pages: 1377-4
  • DOI: 10.1186/s12936-016-1377-4
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Ca(2+) monitoring in Plasmodium falciparum using the yellow cameleon-Nano biosensor (2016)
  • Author(s): Pandey K, Ferreira PE, Ishikawa T, Nagai T, Kaneko O, Yahata K
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 23454-23454
  • DOI: 10.1038/srep23454
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Asada M, Yahata K, Hakimi H, Yokoyama N, Igarashi I, Kaneko O, Suarez CE, Kawazu SI. Transfection of Babesia bovis by double selection with WR99210 and Blasticidin-S and its application for functional analysis of thioredoxin peroxidase-1 (2015)
  • Author(s): Asada M, Yahata K, Hakimi H, Yokoyama N, Igarashi I, Kaneko O, Suarez CE, Kawazu SI
  • Journal Title: PLOS One Volume: 10(5) Issue: 5 Pages: e0125993-e0125993
  • DOI: 10.1371/journal.pone.0125993
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel hemagglutinating, hemolytic and cytotoxic activities of the intermediate subunit of Entamoeba histolytica lectin (2015)
  • Author(s): Kato K, Yahata K, Gopal Dhoubhadel B, Fujii Y, Tachibana H
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 13901-13901
  • DOI: 10.1038/srep13901
  • NAID: 120006986919
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Isolation of invasive Plasmodium yoelii merozoites with a long half-life to evaluate invasion dynamics and potential invasion inhibitors. (2015)
  • Author(s): Mutungi JK, Yahata K, Sakaguchi M, Kaneko O.
  • Journal Title: Molecular and Biochemical Parasitology Volume: 204 Issue: 1 Pages: 26-33
  • DOI: 10.1016/j.molbiopara.2015.12.003
  • Peer Reviewed / Open Access
• [Journal Article] The cytoplasmic region of Plasmodium falciparum SURFIN4.2 is required for transport from Maurer's clefts to the red blood cell surface (2015)
  • Author(s): Kagaya W, Miyazaki S, Yahata K, Ohta N, Kaneko O
  • Journal Title: Tropical Medicine and Health Volume: 43(4) Issue: 4 Pages: 265-272
  • DOI: 10.2149/tmh.2015-38
  • NAID: 130005130397
  • Peer Reviewed / Open Access
• [Presentation] マラリア原虫メロゾイトの滑走運動 (2019)
  • Author(s): 矢幡一英、Moritz Treeck、麻田正仁、金子修
  • Organizer: 第88回日本寄生虫学会大会
• [Presentation] Evaluation methods for parasite egress inhibition for Plasmodium falciparum (2018)
  • Author(s): Kazuhide Yahata、Masahito Asada、Osamu Kaneko
  • Organizer: ICOPA 2018
  • Int'l Joint Research
• [Presentation] Molecular signaling during RBC invasion by malaria parasites (2018)
  • Author(s): Kazuhide Yahata、Masahito Asada、Osamu Kaneko
  • Organizer: Forum Cheju-20
  • Int'l Joint Research
• [Presentation] Evaluation methods for parasite egress inhibition for Plasmodium falciparum (2018)
  • Author(s): Kazuhide Yahata、Masahito Asada、Osamu Kaneko
  • Organizer: The 17th Awaj International Forum on Infection and Immunity
  • Int'l Joint Research
• [Presentation] 熱帯熱マラリア原虫のメロゾイト放出における阻害評価法の確立 (2017)
  • Author(s): 矢幡一英、麻田正仁、金子修
  • Organizer: 第86回日本寄生虫学会大会
• [Presentation] ローデントマラリア原虫のメロゾイト精製法と赤血球侵入機構の解明 (2016)
  • Author(s): 矢幡一英、Mutungi J. Kimanthi、坂口美亜子、金子修
  • Organizer: 第72 回日本寄生虫学会西日本支部大会
  • Place of Presentation: 岐阜大学サテライトキャンパス（岐阜県・岐阜市）
• [Presentation] Ca2+ monitoring in Plasmodium falciparum cytosol through yellow cameleon-Nano biosensor (2015)
  • Author(s): Yahata K, Pandey K, Ferreira PE, Ishikawa T, Kaneko O
  • Organizer: Protein Island Matsuyama International Symposium 2015
  • Place of Presentation: 松山市男女共同参画推進センター、愛媛県松山市
  • Year and Date: 2015-09-24
  • Int'l Joint Research
• [Presentation] Calcium monitoring in Plasmodium falciparum through Yellow Cameleon-Nano Biosensors (2015)
  • Author(s): Yahata K, Pandey K, Ferreira PE, Ishikawa T, Kaneko O
  • Organizer: The 14th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路夢舞台国際会議場、兵庫県淡路市
  • Year and Date: 2015-09-08
  • Int'l Joint Research
• [Presentation] Calcium monitoring in Plasmodium falciparum through Yellow Cameleon-Nano Biosensors (2015)
  • Author(s): 矢幡一英
  • Organizer: 第1回感染症イメージングシンポジウム -基礎と応用-
  • Place of Presentation: 長崎大学グローバルヘルス総合研究棟、長崎県長崎市
  • Year and Date: 2015-06-04
• [Book] 臨床と研究 (2016)
  • Author(s): 矢幡一英、外川祐人、金子修
  • Total Pages: 5
  • Publisher: 大道学館