Analysis of the roles of thioredoxin peroxidase family for adaptation to oxidative stresses in malaria parasites

• Project/Area Number: 23390098
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Parasitology (including Sanitary zoology)
• Research Institution: Obihiro University of Agriculture and Veterinary Medicine
• Principal Investigator: KAWAZU Shin-ichiro 帯広畜産大学, 原虫病研究センター, 教授 (60312295)
• Co-Investigator(Kenkyū-buntansha): KAWAI Satoru 獨協医科大学, 医学部, 准教授 (70275733)
• Co-Investigator(Renkei-kenkyūsha): KANUKA Hirotaka 東京慈恵会医科大学, 医学部, 教授 (50342770)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000); Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2011: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
• Keywords: 感染症 / マラリア / ストレス / レドックス / 遺伝子改変原虫

Research Abstract

Phenotypes observed in the rodent malaria parasite Plasmodium berghei carrying a targeted knockout of thioredoxin peroxidase-family genes (2-Cys Prx KO and 1-Cys Prx KO) were investigated and have the following results: (1) Expression profiling of Prx mRNAs in 2-Cys Prx KO in the hepatic stage: qRT-PCR analysis revealed overexpression of other Prx mRNAs in the populations, indicating a mechanism underlying the response to oxidative stress in the hepatic-stage. (2) Defect in the hepatic-stage development of 2-Cys Prx KO: IFA analysis displayed smaller sized and fewer merozoite formation in the schizont than the parent strain (WT). (2) Defect in the blood-stage development of 1-Cys Prx KO: mice experiments showed lower parasite density of about 1-5% in the population than WT (>20%) during the first 7 days of infection.

Research Products

• [Journal Article] Molecular epidemiology of the emerging human malaria parasite "Plasmodium knowlesi" (2014)
  • Author(s): Hakimi, H., Kawai, S., and Kawazu, S
  • Journal Title: Trop. Parasitol Volume: 4(1) Issue: 1 Pages: 20-24
  • DOI: 10.4103/2229-5070.129154
  • Peer Reviewed
• [Journal Article] An interplay between 2 signaling pathways: melatonin-cAMP and IP3-Ca2+ signaling pathways control intraerythrocytic development of the malaria parasite Plasmodium falciparum. (2014)
  • Author(s): Furuyama, W., Enomoto, M., Mossaad, E., Kawai, S., Mikoshiba, K and Kawazu, S.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 446(1) Issue: 1 Pages: 125-131
  • DOI: 10.1016/j.bbrc.2014.02.070
  • Peer Reviewed
• [Journal Article] Identification of a novel and unique transcription factor in the intraerythrocytic stage of Plasmodium falciparum. (2013)
  • Author(s): Komaki-Yasuda, K., Okuwaki, M., Nagata, K., Kawazu, S., and Kano, S.
  • Journal Title: PLoS One. Volume: 8 Issue: 9 Pages: e74701-e74701
  • DOI: 10.1371/journal.pone.0074701
  • Peer Reviewed
• [Journal Article] Development of Monoclonal Antibodies That Target 1-Cys Peroxiredoxin and Differentiate <i>Plasmodium falciparum</i> from <i>P. vivax</i> and <i>P. knowlesi</i> (2013)
  • Author(s): Hakimi, H., Nguyen, TT., Suganuma, K., Masuda-Suganuma, H., Angeles, JM., Inoue, N., and Kawazu, S
  • Journal Title: Tropical Medicine and Health Volume: 41 Issue: 2 Pages: 55-59
  • DOI: 10.2149/tmh.2012-30
  • NAID: 10031184626
  • ISSN: 1348-8945, 1349-4147
  • Peer Reviewed
• [Journal Article] Expression profiles of peroxiredoxins in liver stage of the rodent malari a parasite Plasmodium berghei (2013)
  • Author(s): Usui M, Masuda-Suganuma H, Fukumoto S, Angeles JM, Inoue N, Kawazu S.
  • Journal Title: Parasitology International Volume: Volume 62 Issue: 3 Pages: 337-340
  • DOI: 10.1016/j.parint.2012.11.007
  • Peer Reviewed
• [Journal Article] 2-Cys peroxiredoxin of Plasmodium falciparum is involved in resistance to heat stress of the parasite (2013)
  • Author(s): Kimura, R., Komaki-Yasuda, K., Kawazu, S., and Kano, S
  • Journal Title: Parasitol. Int Volume: 62(2) Issue: 2 Pages: 137-143
  • DOI: 10.1016/j.parint.2012.11.005
  • Peer Reviewed
• [Journal Article] Expression of cytosolic peroxiredoxins in Plasmodium berghei ookinetes is regulated by environmental factors in the mosquito bloodmeal (2013)
  • Author(s): Turturice, BA., Lamm, MA., Tasch, JJ., Zalewski, A., Kooistra, RL., Schroeter, EH., Sharma, S., Kawazu, SI., and Kanzok SM
  • Journal Title: PLoS Pathog Volume: 9(1) Issue: 1 Pages: e1003136-e1003136
  • DOI: 10.1371/journal.ppat.1003136
  • Peer Reviewed
• [Journal Article] Characterization of the Population Demographics and the MSP-1 Block 2 Allele Gene Frequencies of <i>P. falciparum</i> Infected Individuals in Davao, Philippines (2013)
  • Author(s): Mirano-Bascos, D. et al
  • Journal Title: Tropical Medicine and Health Volume: 41 Issue: 1 Pages: 1-6
  • DOI: 10.2149/tmh.2012-01
  • NAID: 10031164629
  • ISSN: 1348-8945, 1349-4147
  • Peer Reviewed
• [Journal Article] Plasmodium vivax and Plasmodium knowlesi: Cloning, expression and functional analysis of 1-Cys peroxiredoxin (2012)
  • Author(s): Hakimi, H., Asada, M., Angeles, JM., Kawai, S., Inoue, N., and Kawazu, S
  • Journal Title: Exp. Parasitol Volume: 133(1) Issue: 1 Pages: 101-105
  • DOI: 10.1016/j.exppara.2012.10.018
  • Peer Reviewed
• [Journal Article] Mitochondrial peroxidase TPx-2 is not essential in the blood and insect stages of Plasmodium berghei. (2012)
  • Author(s): Masuda-Suganuma, H., Usui, M., Fukumoto, S., Inoue, N.Kawazu, S.
  • Journal Title: Parasit Vectors Volume: 5 Issue: 1 Pages: 252-252
  • DOI: 10.1186/1756-3305-5-252
  • Peer Reviewed
• [Journal Article] Coning and characterization of Plasmodium vivax thioredoxin peroxidase-1 (2012)
  • Author(s): Hakimi, H., Asada, M., Angeles, JM., Inoue, N., and Kawazu, S
  • Journal Title: Parasitol. Res Volume: 111(2) Issue: 2 Pages: 525-529
  • DOI: 10.1007/s00436-012-2864-3
  • Peer Reviewed
• [Journal Article] Gliding Motility of Babesia bovis Merozoites Visualized by Time-Lapse Video Microscopy (2012)
  • Author(s): Asada, M., Goto, Y., Yahata, K., Yokoyama, N., Kawai, S., Inoue, N., Kaneko, O., and Kawazu, S.-I
  • Journal Title: PLoS ONE Volume: 7 Issue: 4 Pages: e35227-e35227
  • DOI: 10.1371/journal.pone.0035227
  • Peer Reviewed
• [Journal Article] In vitro and in vivo antimalarial activities of T-2307, a novel arylamidine. (2012)
  • Author(s): Kimura, A., Nishikawa, H., Nomura, N., Mitsuyama, J., Fukumoto, S., Inoue, N.Kawazu, S.
  • Journal Title: Antimicrob Agents Chemother Volume: 56 Issue: 4 Pages: 2191-3
  • DOI: 10.1128/aac.05856-11
  • Peer Reviewed
• [Journal Article] Improvement of the observational method for Plasmodium berghei oocysts in the midgut of mosquitoes (2011)
  • Author(s): Usui, M. Fukumoto, S. Inoue, N. Kawazu, S.
  • Journal Title: Parasit Vectors Volume: 4 Issue: 1 Pages: 118-118
  • DOI: 10.1186/1756-3305-4-118
  • Peer Reviewed
• [Presentation] 1-Cys 型ペルオキシレドキシン遺伝子欠損Plasmodium berghei の作製と表現型解析 (2014)
  • Author(s): 増田-菅沼裕乃, 他
  • Organizer: 第83回日本寄生虫学会
  • Place of Presentation: 愛媛大学城北キャンパス
  • Year and Date: 2014-03-28
• [Presentation] ドキシンペルオキシダーゼ-1遺伝子欠損がPlasmodium berghei肝臓型の発育に及ぼす影響の解析 (2014)
  • Author(s): 薄井美帆、増田-菅沼裕乃、麻田正仁、福本晋也、井上 昇、河津信一郎
  • Organizer: 第83回日本寄生虫学会
  • Place of Presentation: 愛媛大学 城北キャンパス
• [Presentation] 1-Cys型ペルオキシレドキシン遺伝子欠損Plasmodium bergheiの作製と表現型解析 (2014)
  • Author(s): 増田-菅沼裕乃、薄井美帆、福本晋也、Hassan Hakimi、井上昇、河津信一郎
  • Organizer: 第83回日本寄生虫学会
  • Place of Presentation: 愛媛大学 城北キャンパス
• [Presentation] Development of monoclonal antibodies against Plasmodium falciparum thioredoxin peroxidase 1 and its possible application for malaria diagnosis. (2014)
  • Author(s): Hakimi, H., Goto, Y., Suganuma, K., Angeles, JM., Kawai, S., Inoue, N., and Kawazu, S.
  • Organizer: 第83回日本寄生虫学会
  • Place of Presentation: 愛媛大学 城北キャンパス
• [Presentation] 熱帯熱マラリア原虫の新規転写因子PREBPの性状 (2014)
  • Author(s): 駒木-安田加奈子、奥脇暢、永田恭介、河津 信一郎、狩野 繁之
  • Organizer: 第83回日本寄生虫学会
  • Place of Presentation: 愛媛大学 城北キャンパス
• [Presentation] Expression profiles of peroxiredoxins in liver stage of the rodent malaria parasite Plasmodium berghei (2013)
  • Author(s): Usui, M., et al.
  • Organizer: American Society of Tropical Medicine and Hygiene 62^<th> Annual Meeting(第62回米国熱帯医学会年会)
  • Place of Presentation: Marriot Wardman Park Washington, Washington, DC(ワシントンDC、米国)
  • Year and Date: 2013-11-15
• [Presentation] Plasmodium vivax and P. knowlesi: Cloning, expression and functional analysis of peroxiredoxins (2013)
  • Author(s): Hakimi, H., and Kawazu, S
  • Organizer: International Malaria Symposium (マラリア国際シンポジウム)
  • Place of Presentation: Novotel Hotel, Kota Kinabalu, Malaysia(コタキナバル、マレーシア)
  • Year and Date: 2013-04-16
• [Presentation] 熱帯熱マラリア原虫の薬剤耐性メカニズム (2013)
  • Author(s): 河津信一郎
  • Organizer: 第155回日本獣医学会学術集会
  • Place of Presentation: 東京大学駒場キャンパス
  • Year and Date: 2013-03-28
• [Presentation] Expression profiles of peroxiredoxins in liver stage of the rodent malaria parasite Plasmodium berghei. (2013)
  • Author(s): Usui, M., Masuda-Suganuma, H., Fukumoto, S., Angeles, JMA., Inoue, N., Kanzok, MS., and Kawazu, S.
  • Organizer: American Society of Tropical Medicine and Hygiene 62th Annual Meeting 第62回米国熱帯医学会年会
  • Place of Presentation: Marriot Wardman Park Washington, Washington, DC（ワシントンDC、米国）
• [Presentation] Plasmodium vivax and P. knowlesi: Cloning, expression and functional analysis of peroxiredoxins. (2013)
  • Author(s): Hakimi, H., and Kawazu, S.
  • Organizer: International Malaria Symposium マラリア国際シンポジウム
  • Place of Presentation: Novotel Hotel, Kota Kinabalu, Malaysia（コタキナバル、マレーシア）
  • Invited
• [Presentation] Development of monoclonal antibodies targeting 1-Cys peroxiredoxin which differentiate Plasmodium falciparum from P. vivax and P. knowlesi. (2013)
  • Author(s): Hakimi, H. et al.
  • Organizer: 第82回日本寄生虫学会大会
  • Place of Presentation: 東京医科歯科大学 湯島キャンパス
• [Presentation] 熱帯熱マラリア原虫の新規転写因子PREBP (Prx regulatory element binding protein)の活性の解析 (2013)
  • Author(s): 駒木-安田加奈子 他
  • Organizer: 第82回日本寄生虫学会大会
  • Place of Presentation: 東京医科歯科大学 湯島キャンパス
• [Presentation] ローデントマラリア原虫肝内型におけるペルオキシレドキシンの発現プロファイル (2013)
  • Author(s): 薄井美帆 他
  • Organizer: 第82回日本寄生虫学会大会
  • Place of Presentation: 東京医科歯科大学 湯島キャンパス
• [Presentation] Plasmodium vivax and P. knowlesi: Cloning, expression and functional analysis of 1-Cys peroxiredoxin. (2013)
  • Author(s): Hakimi, H. et al.
  • Organizer: 第155回日本獣医学会学術集会
  • Place of Presentation: 東京大学 駒場キャンパス
• [Presentation] 熱帯熱マラリア原虫の薬剤耐性メカニズム (2013)
  • Author(s): 河津信一郎
  • Organizer: 第155回日本獣医学会学術集会
  • Place of Presentation: 東京大学 駒場キャンパス
  • Invited
• [Presentation] ミトコンドリア局在ペルオキシダーゼ(TPx-2)ノックアウトがマラリア原虫の発育に及ぼす影響の解析 (2012)
  • Author(s): 薄井美帆, 他
  • Organizer: 第80回日本寄生虫学会大会
  • Place of Presentation: 東京慈恵会医科大学
  • Year and Date: 2012-07-17
• [Presentation] Plasmodium vivax and P. knowlesi: Cloning, expression and functional analysis of 1-Cys peroxiredoxin. (2012)
  • Author(s): Hakimi, H. et al.
  • Organizer: JITMM2012 & FBPZ7 2012合同国際熱帯医学会および第７回人獣共通寄生虫症セミナー
  • Place of Presentation: Centara Grand & Bangkok Convention Centre at Central World, Bangkok（バンコク、タイ王国）
  • Invited
• [Presentation] Plasmodium vivax and P. knowlesi: cloning, expression and functional analysis of 1-Cys peroxiredoxin. (2012)
  • Author(s): Hakimi, H. et al.
  • Organizer: American Society of Tropical Medicine and Hygiene 61th Annual Meeting 第61回米国熱帯医学会年会
  • Place of Presentation: Atlanta Marriot Marquis（アトランタ、米国）
• [Presentation] 熱帯熱マラリア原虫のpf1-cys-prxn遺伝子の5’領域cis-elementに結合する新規核内因子は転写の活性化に関与する (2012)
  • Author(s): 駒木-安田加奈子 他
  • Organizer: 第10回分子寄生虫学マラリア研究フォーラム
  • Place of Presentation: 群馬大学
• [Presentation] Development of monoclonal antibodies targeting 1-Cys peroxiredoxin which differentiate Plasmodium falciparum from P. vivax and P. knowlesi. (2012)
  • Author(s): Hakimi, H. et al.
  • Organizer: 第53回日本熱帯医学会大会
  • Place of Presentation: 帯広市 とかちプラザ
• [Presentation] Expression profiles of peroxiredoxins in liver stage of the rodent malaria parasite Plasmodium berghei. (2012)
  • Author(s): Usui, M. et al.
  • Organizer: 5th ASEAN Congress of Tropical Medicine and Parasitology 第5回ASEAN熱帯医学寄生虫学会議
  • Place of Presentation: Citystate Tower Hotel, Manila（マニラ、フィリピン共和国）
• [Presentation] 熱帯熱マラリア原虫pf-1-cys-prx遺伝子cis-elementに結合する新規核内因子の性状の解析 (2012)
  • Author(s): 駒木-安田加奈子 他
  • Organizer: 第81回日本寄生虫学会大会
  • Place of Presentation: 兵庫医科大学 西宮キャンパス
• [Presentation] Cloning and characterization of Plasmodium vivax thioredoxin peroxidase-1. (2011)
  • Author(s): Hakimi, H. et al.
  • Organizer: American Society of Tropical Medicine and Hygiene 60th Annual Meeting 第61回米国熱帯医学会年会
  • Place of Presentation: Marriot Downtown Philadelphia（フィラデルフィア、米国）
• [Presentation] Cloning and characterization of Plasmodium vivax thioredoxin peroxidase-1. (2011)
  • Author(s): Hakimi, H. et al.
  • Organizer: The 17 th Japanese-German Symposium on Protozoan Diseases 第17回日独原虫病シンポジウム
  • Place of Presentation: 奈良女子大学
• [Presentation] ミトコンドリア局在ペルオキシダーゼ（TPx-2）ノックアウトがマラリア原虫の発育に及ぼす影響の解析 (2011)
  • Author(s): 薄井美帆 他
  • Organizer: 第80回日本寄生虫学会大会
  • Place of Presentation: 東京慈恵会医科大学
• [Remarks]
  • URL: http://www.obihiro.ac.jp/~tryp/index.html
• [Remarks] Kawazu Laboratory, NRCPD
  • URL: http://www.obihiro.ac.jp/~tryp/index.html
• [Remarks] 河津研究室ホームページ
  • URL: http://www.obihiro.ac.jp/~tryp/index.html
• [Remarks] 河津研究室ホームページ
  • URL: http://www.obihiro.ac.jp/~tryp/index.html