Molecular and functional characterization of glucose transporter genes of the fox tapeworm Echinococcus multilocularis

• Project/Area Number: 15K08454
• 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: Nihon University
• Principal Investigator: MATSUMOTO Jun 日本大学, 生物資源科学部, 准教授 (70296169)
• Co-Investigator(Kenkyū-buntansha): 孝口 裕一 北海道立衛生研究所, その他部局等, 主査 (50435567) ; 上家 潤一 麻布大学, 獣医学部, 准教授 (10400269)
• Research Collaborator: YAGI Kinpei ; KASHIDE Takuya
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: エキノコックス / グルコース / トランスポーター / 寄生虫 / 蠕虫 / エネルギー代謝 / 寄生適応

Outline of Final Research Achievements

Echinococcus multilocularis is a zoonotic parasite, causing serious health problems in animals and humans. The parasite lacks a digestive tract and absorbs essential nutrients, including glucose, across the syncytial tegument on its external surface. We characterized glucose transporter homologues from E. multilocularis. As a result, we obtained full-length sequences of 2 putative glucose transporter genes (EmGLUT1 and EmGLUT2). Functional expression analysis using Xenopus oocytes demonstrated clear uptake of glucose by EmGLUT1, but not by EmGLUT2. Further analyses revealed that glucose uptake of EmGLUT1 did not depend on the presence of Na+ nor H+, respectively. Immunoblot analyses demonstrated that both EmGLUTs were stably expressed during each developmental stage of the parasite. We conclude that EmGLUT1 is a simple facilitated glucose transporter and possibly plays an important role in glucose uptake by E. multilocularis throughout its life cycle.

Academic Significance and Societal Importance of the Research Achievements

エキノコックス（Em）の人獣に対する主要な病害は、幼虫期の活発な増殖に起因する。Emのグルコース摂取機構は、虫体の活発な増殖を支えるエネルギー代謝機構の根幹をなすものであり、したがって、虫体増殖による疾病を制御するためのアキレス腱であると考えられる。そのグルコース摂取に関わる分子機構の一部を初めて明らかにした点に、本研究の学術的な意義がある。本研究で対象としたEm とその近縁寄生虫類は、人体のみならず様々な家畜や伴侶動物にも寄生し、世界中で深刻な被害をもたらしている。本研究により得られた知見は、近縁寄生虫類による疾病の制御への波及効果も期待される。

Research Products

• [Journal Article] Intestinal echinococcosis in a pet dog from Missouri (2019)
  • Author(s): Kuroki, K., Morishima, Y., Neil, J., Beerntsen, B., Matsumoto, J., and Stich, B.
  • Journal Title: Journal of the American Veterinary Medical Association Volume: －
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Molecular and functional characterization of glucose transporter genes of the fox tapeworm Echinococcus multilocularis. (2018)
  • Author(s): Kashiide Takuya, Kikuta Shingo, Yamaguchi Misaki, Irie Takao, Kouguchi Hirokazu, Yagi Kinpei, Matsumoto Jun.
  • Journal Title: Molecular and Biochemical Parasitology Volume: 225 Pages: 7-14
  • DOI: 10.1016/j.molbiopara.2018.08.004
  • Peer Reviewed
• [Journal Article] Prevalence and molecular subtyping of Blastocystis from dairy cattle in Kanagawa, Japan (2018)
  • Author(s): Masuda, A., Sumiyoshi, T., Ohtaki, T., and Matsumoto, J.
  • Journal Title: Parasitology International Volume: 67 Issue: 6 Pages: 702-705
  • DOI: 10.1016/j.parint.2018.07.005
  • Peer Reviewed
• [Journal Article] Gene expression profiles of the small intestinal mucosa of dogs repeatedly infected with the cestode Echinococcus multilocularis (2018)
  • Author(s): Kouguchi, H., Irie, T., Matsumoto, J., Furuoka, H., Ishiwata, K., Nakao, R., and Yagi, K.
  • Journal Title: Data in Brief Volume: 17 Pages: 180-183
  • DOI: 10.1016/j.dib.2018.01.004
  • Peer Reviewed / Open Access
• [Journal Article] Successful intestinal Echinococcus multilocularis oncosphere invasion and establishment in resistant RccHanTM:WIST rats after pharmacological immunosuppression (2016)
  • Author(s): Armua-Fernandez, M. T., Joekel, D., Schweiger, A., Eichenberger, R. M., Matsumoto, J., and Deplazes, P
  • Journal Title: Parasitology Volume: 143 Issue: 10 Pages: 1252-1260
  • DOI: 10.1017/s0031182016000809
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The timing of worm exclusion in dogs repeatedly infected with the cestode Echinococcus multilocularis (2016)
  • Author(s): Kouguchi H, Irie T, Matsumoto J, Nakao R, Sugano Y, Oku Y, Yagi K
  • Journal Title: J Helminthol Volume: 90 Issue: 6 Pages: 766-772
  • DOI: 10.1017/s0022149x15001169
  • Peer Reviewed
• [Presentation] エキノコックスとの遭遇に備えて. 知っておくべき 大切なポイント (2019)
  • Author(s): 松本 淳
  • Organizer: 第15回日本獣医内科学アカデミー学術大会
  • Invited
• [Presentation] エキノコックス症対策における獣医師の役割 (2018)
  • Author(s): 松本 淳
  • Organizer: 平成２９年度日本獣医師会獣医学術学会年次大会
• [Presentation] Echinococcus multilocularis 根室株の虫卵感染マウスにおけるマイクロRNA解析 (2017)
  • Author(s): 今里裕平, 中尾 亮, 入江隆夫, 孝口裕一, 松本 淳, 八木欣平, 片倉 賢
  • Organizer: 第８６回日本寄生虫学会大会
• [Presentation] 多包条虫のグルコース摂取・代謝機構解明を目指して － PEPCKのクローニングと機能解析 － (2016)
  • Author(s): 山口美咲, 松本 淳
  • Organizer: 第10回蠕虫研究会
  • Place of Presentation: ハートピア熱海（静岡県・熱海市）
  • Year and Date: 2016-11-18
• [Presentation] 幼虫期 Echinococcus multilocularis 根室株のmiRNA解析 (2016)
  • Author(s): 今里裕平, 中尾 亮, 入江隆夫, 孝口裕一, 松本 淳, 八木欣平, 片倉 賢
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 日本大学生物資源科学部（神奈川県・藤沢市）
  • Year and Date: 2016-09-07
• [Presentation] Characterization of glucose transporter genes from fox tapeworm Echinococcus multiocularis (2015)
  • Author(s): Kashiide T, Kikuta S, Yamaguchi M, Kato T, Irie T, Kouguchi H, Yagi K, Matsumoto J
  • Organizer: Molecular and Cellular Biology of Helminth Parasites IX
  • Place of Presentation: Hydra, Greece
  • Year and Date: 2015-08-31
  • Int'l Joint Research
• [Presentation] Molecular and functional characterization of glucose transporter genes from Echinococcus multilocularis (2015)
  • Author(s): Kashiide T, Kikuta S, Yamaguchi M, Kato T, Irie T, Kouguchi H, Yagi K, Matsumoto J
  • Organizer: 25th International Conference of the World Association for the Advancement of Veterinary Parasitology
  • Place of Presentation: Liverpool, UK
  • Year and Date: 2015-08-16
  • Int'l Joint Research
• [Presentation] 多包条虫 Echinococcus multilocularis 由来 ホスホエノールピルビン酸カルボキシキナーゼ遺伝子のクローニング (2015)
  • Author(s): 山口 美咲、樫出 拓哉、松本 淳
  • Organizer: 第53回日本大学獣医学会
  • Place of Presentation: 日本大学生物資源科学部（藤沢市）
  • Year and Date: 2015-06-28
• [Book] 犬と猫の検査・手技ガイド 2019「エキノコックス症」（分担） (2019)
  • Author(s): 松本 淳
  • Total Pages: 821
  • Publisher: インターズー
  • ISBN: 9784866710594
• [Book] Echinococcosis (Chapter 5: Medical treatment of Echinococcus multilocularis and new horizons for drug discovery: characterization of mitochondrial complex II as a potential drug target) (2017)
  • Author(s): Enkai, S., Sakamoto, K., Kaneko, M., Kouguchi, H., Irie, T., Yagi, K., Ishida, Y., Matsumoto, J., Oku, Y., Katakura, K., Fujita, O., Nozaki, T., and Kita, K.
  • Total Pages: 69
  • Publisher: IntechOpen Limited
  • ISBN: 9789535135920
• [Book] Medical treatment of Echinococcus multilocularis and new horizons for drug discovery: Characterization of mitochondrial complex II as a potential drug target. In: Echinococcosis (Tnay Inceboz, ed.) (2017)
  • Author(s): Enkai, S., Sakamoto, K., Kaneko, M., Kouguchi, H., Irie, T., Yagi, K., Matsumoto, J., Oku, Y., Katakura, K., Fujita, O., Nozaki, T., and Kita, K
  • Publisher: InTech