Longistatin secretion in tick feeding process and its application to disease control

• Project/Area Number: 17H03919
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Kitasato University
• Principal Investigator: Hatta Takeshi 北里大学, 医学部, 講師 (00455304)
• Co-Investigator(Kenkyū-buntansha): 中尾 亮 北海道大学, 獣医学研究院, 准教授 (50633955) ; 白藤 梨可 帯広畜産大学, 原虫病研究センター, 助教 (00549909)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: フタトゲチマダニ / ロンギスタチン / アクチン / 翻訳伸長因子 / プロモーター配列 / レポーターアッセイ / マダニ / 転写因子 / 遺伝子強制発現 / プロモーター / Hypoxia inducible factor / 唾液分子 / RNAseq / 唾液 / 吸血生理 / 病原体媒介

Outline of Final Research Achievements

This study is focusing on the biologically active molecules such as salivary molecules of Haemaphysalis longicornis tick which can transmit many kinds of the infectious disease to human and animals. In particular, we attempted to elucidate the biological significance related to the secretion of those bioactive molecules. Using a next-generation sequencer, we have elucidated the sequence of the promoter region involved in the expression control of functional molecules of ticks such as longistatin, and succeeded in identifying the translation elongation factor promoter sequence region with a particularly strong transcription activity.

Academic Significance and Societal Importance of the Research Achievements

重症熱性血小板減少症候群ウイルスのベクターとされるフタトゲチマダニでは、未だ培養細胞や遺伝子解析のためのツールが少ない。今回解読に成功した翻訳伸長因子プロモーター配列領域は、例えばゲノム編集に必須のCas9蛋白質をマダニ体内にて独自に発現させることが期待される等、外来遺伝子の発現に用いることが期待でき、将来的にはマダニ研究ツールの基盤エレメントとなることが予想され、学術的にも社会的にもインパクトの大きい成果である。

Research Products

• [Journal Article] マダニの人工吸血～過去・現在・未来～ (2020)
  • Author(s): 八田岳士
  • Journal Title: 衛生動物 Volume: 71(1) Pages: 15-23
  • Peer Reviewed
• [Journal Article] Characterization of the RAGE-binding protein, Strongyloides venestatin, produced by the silkworm-baculovirus expression system. (2019)
  • Author(s): Tsubokawa D, Lee JM, Hatta T, Mikami F, Maruyama H, Arakawa T, Kusakabe T, Tsuji N
  • Journal Title: Infect Genet Evol Volume: 75 Pages: 103964-103964
  • DOI: 10.1016/j.meegid.2019.103964
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization of an iron-inducible Haemaphysalis longicornis tick-derived promoter in an Ixodes scapularis-derived tick cell line (ISE6). (2019)
  • Author(s): Hernandez EP, Kusakisako K, Hatta T, Tanaka T.
  • Journal Title: Parasit Vectors. Volume: 12(1) Issue: 1 Pages: 321-321
  • DOI: 10.1186/s13071-019-3574-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transovarial persistence ofBabesia ovata DNA in a hard tick, Haemaphysalis longicornis, in a semi-artificialmouse skin membrane feeding system. (2018)
  • Author(s): Umemiya-Shirafuji R, Hatta T, Okubo K, Sato M, Maeda H, Kume A, Yokoyama N,Igarashi I, Tsuji N, Fujisaki K, Inoue N, Suzuki H.
  • Journal Title: Acta Parasitol. Volume: 63 Issue: 2 Pages: 433-433
  • DOI: 10.1515/ap-2018-0051
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Glutathione S-transferases play a role in the detoxification offlumethrin and chlorpyrifos in Haemaphysalis longicornis (2018)
  • Author(s): Hernandez EP, Kusakisako K, Talactac MR, Galay RL, Hatta T, Fujisaki K, Tsuji N, Tanaka T.
  • Journal Title: Parasit Vectors. Volume: 11 Issue: 1 Pages: 460-460
  • DOI: 10.1186/s13071-018-3044-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] NovelCharacteristics of Mitochondrial Electron Transport Chain from Eimeria tenella (2018)
  • Author(s): Matsubayashi M, Inaoka DK, Komatsuya K, Hatta T, Kawahara F, Sakamoto K,Hikosaka K, Yamagishi J, Sasai K, Shiba T, Harada S, Tsuji N, Kita K.
  • Journal Title: Genes (Basel) Volume: 10 Issue: 1 Pages: 1-1
  • DOI: 10.3390/genes10010029
  • Peer Reviewed / Open Access
• [Journal Article] Characterization and expression analysis of a newly identified glutathione S-transferase of the hard tick Haemaphysalis longicornis during blood-feeding (2018)
  • Author(s): Hernandez Emmanuel Pacia、Kusakisako Kodai、Talactac Melbourne Rio、Galay Remil Linggatong、Hatta Takeshi、Matsuo Tomohide、Fujisaki Kozo、Tsuji Naotoshi、Tanaka Tetsuya
  • Journal Title: Parasites & Vectors Volume: 11 Issue: 1 Pages: 91-91
  • DOI: 10.1186/s13071-018-2667-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] First detection and molecular identification of Entamoeba bovis from Japanese cattle (2018)
  • Author(s): Makoto Matsubayashi, Yuu Matsuura, Satoko Nukata, Yuusuke Daizi, Tomoyuki Shibahara, Isao Teramoto, Tomohide Matsuo, Shigehiko Uni, Takeshi Hatta, Akira Kaneko, Naotoshi Tsuji, Kazumi Sasai.
  • Journal Title: Parasitology Research Volume: 117(1) Issue: 1 Pages: 339-342
  • DOI: 10.1007/s00436-017-5689-2
  • Peer Reviewed / Open Access
• [Journal Article] Transovarial persistence of Babesia ovata DNA in a hard tick, Haemaphysalis longicornis, in a semi-artificial mouse skin membrane feeding system (2017)
  • Author(s): Umemiya-Shirafuji R, Hatta T, Okubo K, Sato M, Maeda H, Kume A, Yokoyama N, Igarashi I, Tsuji N, Fujisaki K, Inoue N, Suzuki H.
  • Journal Title: Acta Parasitologica Volume: 62 Issue: 4 Pages: 836-841
  • DOI: 10.1515/ap-2017-0100
  • NAID: 120006411416
  • Peer Reviewed / Open Access
• [Journal Article] Application of Percoll density gradient centrifugation for separation of Babesia ovatainfected erythrocytes. (2017)
  • Author(s): Sato M, Hatta T, Maeda H, Tsubokawa D, Alim MA, Tsuji N, Inoue N, Suzuki H, Umemiya-Shirafuji R.
  • Journal Title: J. Protozool. Res. Volume: 27 Pages: 8-12
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Interleukin-13/interleukin-4 receptor pathway is crucial for production of Sd a -sialomucin in mouse small intestinal mucosa by Nippostrongylus brasiliensis infection (2017)
  • Author(s): Tsubokawa Daigo、Ishiwata Kenji、Goso Yukinobu、Nakamura Takeshi、Hatta Takeshi、Ishihara Kazuhiko、Kanuka Hirotaka、Tsuji Naotoshi
  • Journal Title: Parasitology International Volume: 66 Issue: 6 Pages: 731-734
  • DOI: 10.1016/j.parint.2017.08.004
  • Peer Reviewed
• [Journal Article] Venestatin, a Ca++-binding protein from the parasitic nematode Strongyloides venezuelensis, is involved in the larval migration process (2017)
  • Author(s): Tsubokawa D, Hatta T, Kikuchi T, Maeda H, Mikami F, Alim MA, Maruyama H, Tsuji N
  • Journal Title: Int J Parasitol. Volume: in press Issue: 8 Pages: 501-509
  • DOI: 10.1016/j.ijpara.2017.01.008
  • Peer Reviewed / Int'l Joint Research
• [Presentation] ベクターにおける病原体生残戦略の解明 (2020)
  • Author(s): 八田岳士
  • Organizer: 日本大学動物医科学研究センターセミナー
  • Invited
• [Presentation] Glutathione S-transferases are important in oxidative stress management and acaricide metabolism in the hard ticks Haemaphysalis longicornis． (2019)
  • Author(s): Emmanuel Hernandez，草木迫 浩大，Melbourne Talactac，Remil Galay，八田岳士，藤崎幸蔵，辻 尚利，田仲哲也．
  • Organizer: 第161回日本獣医学会学術集会
• [Presentation] Advances of research in triangular relationship among vectors, pathogens and hosts． (2019)
  • Author(s): Takeshi HATTA．
  • Organizer: Joint Symposium Institut Pasteur and The Kitasato Institute Kitasato University
  • Int'l Joint Research / Invited
• [Presentation] 糞線虫の宿主体内移行における終末糖化産物受容体（RAGE）の役割. (2019)
  • Author(s): 坪川大悟、八田岳士、小泉頌歌、三上房子、山本靖彦、丸山治彦、辻尚利.
  • Organizer: 第88回日本寄生虫学会大会
• [Presentation] Characterization of an iron-inducible Haemaphysalis longicornis tick-derived promoter in an Ixodes scapularis derived tick cell line (ISE6). (2019)
  • Author(s): Emmanuel Hernandez, Kodai Kusakisako,Takeshi Hatta, Tetsuya Tanaka.
  • Organizer: 第88回日本寄生虫学会大会
• [Presentation] Haemaphysalis longicornis glutathione S-transferase (HlGST2) is vital in the detoxification of chlorpyrifos in larval ticks (2018)
  • Author(s): Emmanuel Hernandez, 草木迫浩大、Melboune Talactac、Remil Galay、八田岳士、藤崎幸蔵、辻尚利、田仲哲也.
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] ベネスタチン遺伝子ノックダウン糞線虫を用いた感染実験の展開. (2018)
  • Author(s): 坪川大悟、八田岳士、小泉頌歌、三上房子、辻尚利.
  • Organizer: 第26回分子寄生虫学ワークショップ・第16回分子寄生虫・マラリア研究フォーラム合同大会
• [Presentation] マダニ－バベシア実験感染モデルの確立 (2017)
  • Author(s): 前田 大輝、八田 岳士、坪川 大悟、三上 房子、松林 誠、三好 猛晴、白藤(梅宮) 梨可、河津 信一郎、五十嵐 郁男、望月 雅美、辻 尚利、田仲 哲也
  • Organizer: 第160回 日本獣医学会学術集会
• [Presentation] Preliminary study on the development of a model for the complete lifecycle of Babesia ovata without the need for cattle host (2017)
  • Author(s): Takeshi Hatta, Hiroki Maeda, Daigo Tsubokawa, Fusako Mikami, M Abdul Alim, Makoto Matsubayashi, Rika Umemiya-Shirafuji, Ryo Nakao, Naotoshi Tsuji
  • Organizer: 9th Tick and Tick-borne Pathogen Conference & 1st Asia Pacific Rickettsia Conference
  • Int'l Joint Research