Generation of rodent malaria parasite with high mutation rate and confirmation of its usefulness for next generation of malariology

• Project/Area Number: 24590501
• 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: Juntendo University (2014-2015); Gunma University (2012-2013)
• Principal Investigator: Makoto Hirai 順天堂大学, 医学部, 准教授 (50326849)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: mutator malaria / ネズミマラリア原虫 / ミューテーター / 熱帯熱マラリア原虫

Outline of Final Research Achievements

We have succeeded to generate mutator malaria parasite, Plasmodium berghei with destructed proof reading activity in DNA polymerase delta. We confirmed that the mutator malaria parasite shows 80 times higher mutation rate than wild-type parasite. Moreover, we succeeded to isolate several drug resistant parasites from mutator malaria parasite, which could be utilized for further research to reveal molecular mechanisms of parasite drug resistance. A series of these results provide the proof that our mutator parasite could be suitable research tool for parasite biology, especially drug resistance.

Research Products

• [Journal Article] Plasmodium falciparum kelch 13: a potential molecular marker for tackling artemisinin-resistant malaria parasites. (2016)
  • Author(s): Mita T, Tachibana S, Hashimoto M, Hirai M.
  • Journal Title: Expert Rev Anti Infect Ther. Volume: 14 Issue: 1 Pages: 125-135
  • DOI: 10.1586/14787210.2016.1106938
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Visualization of Malaria Parasites in the Skin Using the Luciferase Transgenic Parasite,<i> Plasmodium berghei</i> (2015)
  • Author(s): Matsuoka H, Tomita H, Hattori R, Arai M, Hirai M.
  • Journal Title: Tropical Medicine and Health Volume: 43 Issue: 1 Pages: 53-61
  • DOI: 10.2149/tmh.2014-18
  • NAID: 130004704899
  • ISSN: 1348-8945, 1349-4147
  • Peer Reviewed
• [Journal Article] Direct evidence for the atovaquone action on the Plasmodium cytochrome bc1 complex. (2015)
  • Author(s): Siregar JE, Kurisu G, Kobayashi T, Matsuzaki M, Sakamoto K, Mi-Ichi F, Watanabe Y, Hirai M, Matsuoka H, Syafruddin D, Marzuki S, Kita K.
  • Journal Title: Parasitol Int Volume: 64 Issue: 3 Pages: 295-300
  • DOI: 10.1016/j.parint.2014.09.011
  • Peer Reviewed / Open Access
• [Journal Article] Lactate retards the development of erythrocytic stages of the human malaria parasite Plasmodium falciparum. (2015)
  • Author(s): Hikosaka K, Hirai M, Komatsuya K, Ono Y, Kita K.
  • Journal Title: Parasitol Int Volume: 64 Issue: 3 Pages: 301-303
  • DOI: 10.1016/j.parint.2014.08.003
  • Peer Reviewed / Open Access
• [Journal Article] Plasmodium berghei ANKA causes intestinal malaria associated with dysbiosis (2015)
  • Author(s): Taniguchi T, Miyauchi E, Nakamura S, Hirai M, Suzue K, Imai T, Nomura T, Handa T, Okada H, Shimokawa C, Onishi R, Olia A, Hirata J, Tomita H, Ohno H, Horii T, Hisaeda H
  • Journal Title: Scientific Reports Volume: 5:15699 Issue: 1 Pages: 1-12
  • DOI: 10.1038/srep15699
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Evaluating experimental cerebral malaria using oxidative stress indicator OKD48 mice. (2014)
  • Author(s): Imai T, Iwawaki T, Akai R, Suzue K, Hirai M, Taniguchi T, Okada H, Hisaeda H.
  • Journal Title: Int J Parasitol. Volume: 44 Issue: 10 Pages: 681-685
  • DOI: 10.1016/j.ijpara.2014.06.002
  • Peer Reviewed / Open Access
• [Journal Article] Generation of rodent malaria parasites with a high mutation rate by destructing proofreading activity of DNA polymerase δ. (2014)
  • Author(s): Honma H, Hirai M, Nakamura S, Hakimi H, Kawazu S, Palacpac NM, Hisaeda H, Matsuoka H, Kawai S, Endo H, Yasunaga T, Ohashi J, Mita T, Horii T, Furusawa M, Tanabe K.
  • Journal Title: DNA Res Volume: 21 Issue: 4 Pages: 439-46
  • DOI: 10.1093/dnares/dsu009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Species-specific immunity induced by infection with Entamoeba histolytica and Entamoeba moshkovskii in mice (2013)
  • Author(s): Shimokawa, C., Culleton, R., Imai, T., Suzue, K., Hirai, M., Taniguchi, T., Kobayashi, S., Hisaeda, H., Hamano, S
  • Journal Title: PLoS One Volume: 8(11) Issue: 11 Pages: e82025-e82025
  • DOI: 10.1371/journal.pone.0082025
  • NAID: 120006986684
  • Peer Reviewed
• [Journal Article] IL-23 protection against Plasmodium berghei infection in mice is partially dependent on IL-17 from macrophages (2013)
  • Author(s): Ishida H, Imai T, Suzue K, Hirai M, Taniguchi T, Yoshimura A, Iwakura Y, Okada H, Suzuki T, Shimokawa C, and Hisaeda
  • Journal Title: Eur. J. Immunol. Volume: 43 Issue: 10 Pages: 2696-2706
  • DOI: 10.1002/eji.201343493
  • Peer Reviewed
• [Journal Article] Characterazation of burdock mottle virus, a novel member of the genus Benyvirus, and the presence of benyvirus-related sequences in the plant and insect genomes. (2013)
  • Author(s): Kondo, H. , Hirano, S., Chiba, S., Andika, I.B., Hirai, M., Maeda, T. and Tamada, T.
  • Journal Title: Virus Research Volume: 177 Issue: 1 Pages: 75-86
  • DOI: 10.1016/j.virusres.2013.07.015
  • Peer Reviewed
• [Journal Article] CD8(+) T cell activation by murine erythroblasts infected with malaria parasites. (2013)
  • Author(s): Imai T, Ishida H, Suzue K, Hirai M, Taniguchi T, Okada H, Suzuki T, Shimokawa C, Hisaeda H.
  • Journal Title: Sci Rep. Volume: 3 Issue: 1 Pages: 1572-1572
  • DOI: 10.1038/srep01572
  • NAID: 120006985954
  • Peer Reviewed
• [Journal Article] Resistance to Malaria by Enhanced Phagocytosis of Erythrocytes in LMP7-deficient Mice. (2013)
  • Author(s): Duan X, Imai T, Chou B, Tu L, Himeno K, Suzue K, Hirai M, Taniguchi T, Okada H, Shimokawa C, Hisaeda H.
  • Journal Title: PLoS One. Volume: 8 Issue: 3 Pages: 1-9
  • DOI: 10.1371/journal.pone.0059633
  • Peer Reviewed
• [Journal Article] One Injection of DsRed Followed by Bites from Transgenic Mosquitoes Producing DsRed in the Saliva Elicits a High Titer of Antibody in Mice (2012)
  • Author(s): Matsuoka H, Sano G, Hattori R, Tomita H, Yamamoto DS, Hirai M.
  • Journal Title: Tropical Medicine and Health Volume: 40 Issue: 2 Pages: 47-53
  • DOI: 10.2149/tmh.2011-10
  • NAID: 10031123157
  • ISSN: 1348-8945, 1349-4147
  • Peer Reviewed
• [Journal Article] Critical roles of the mitochondrial complex II in oocyst formation of rodent malaria parasite Plasmodium berghei. (2012)
  • Author(s): Hino A, Hirai M, Tanaka TQ, Watanabe Y, Matsuoka H, Kita K.
  • Journal Title: J Biochem Volume: 152 Issue: 3 Pages: 259-68
  • DOI: 10.1093/jb/mvs058
  • NAID: 10031166137
  • Peer Reviewed
• [Journal Article] Toward understanding the role of mitochondrial complex II in the intraerythrocytic stages of Plasmodium falciparum: gene targeting of the Fp subunit. (2012)
  • Author(s): Tanaka TQ, Hirai M, Watanabe Y, Kita K.
  • Journal Title: Parasitol Int Volume: 61 Issue: 4 Pages: 726-8
  • DOI: 10.1016/j.parint.2012.06.002
  • Peer Reviewed
• [Presentation] 比較トランスクリプトームによるマラリア原虫受精関連因子の探索 (2014)
  • Author(s): 平井 誠、新井 明治 、安彦 真文、本間 一、岡本 龍史、鈴江 一友、今井 孝、谷口 委代、堀井 俊宏、田邉 和裄、久枝 一
  • Organizer: 日本寄生虫学会
  • Place of Presentation: 愛媛県松山市
• [Presentation] 比較トランスクリプトームによるマラリア原虫受精因子の探索 (2012)
  • Author(s): 平井誠、安彦真文、岡本龍司、本間一、鈴江一友、今井孝、堀井俊宏、田邉和裄、久枝一
  • Organizer: 第１０回分子寄生虫・マラリアフォーラム、第７２回日本寄生虫学会東日本支部会合同大会
  • Place of Presentation: 群馬大学医学部
• [Presentation] マラリア原虫をやっつける～その驚異、生態、新たな対策 (2012)
  • Author(s): 平井 誠
  • Organizer: 第2回 WIAS Top Runners’ Lecture Collection of Science
  • Place of Presentation: 早稲田大学
  • Invited
• [Book] 生物の受精 (2014)
  • Author(s): 森稔幸、平井 誠
  • Publisher: 化学と生物
• [Book] Sexual reproduction (2014)
  • Author(s): Makoto Hirai
  • Publisher: Elsevier
• [Remarks] マラリア生物学研究のための新しいツールを開発―マラリア撲滅のための道を拓くー
  • URL: http://www.gunma-u.ac.jp/sb/sb.cgi?eid=829