The establishment for trypanocidal mechanism evaluation assay and application for the development for trypanocidal drugs

• Project/Area Number: 16K18793
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science
• Research Institution: Obihiro University of Agriculture and Veterinary Medicine
• Principal Investigator: SUANUMA KEISUKE 帯広畜産大学, 畜産学部, 助教 (60772184)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: トリパノソーマ / 治療薬 / 新規創薬 / 薬剤開発 / 寄生虫学 / 原虫病

Outline of Final Research Achievements

Human and Animal African trypanosomosis is a neglected tropical disease and causes severe human and economic loss in developing countries. For controlling the disease, development for novel trypanocidal drugs is an urgent issue. In this study, in vitro trypanicidal activity evaluation assays against six pathogenic trypanosomes were developed and trypanicidal activity about 1,000 compounds were evaluated the assays. In addition, to reveal the mode of trypanocidal action of these compounds, transcriptome analyses were also performed. Several compounds showed strong trypaniocidal activity in vitro, and some of them also showed treatment efficacy using in vivo mice model. The development and implementation for novel trypanocidal drugs against trypanosomosis will be expected based on the current study.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義は、ヒトトリパノソーマ症に比べ研究開発が遅れている動物トリパノソーマ症に対する新規薬剤開発のためのin vitro抗トリパノソーマ活性評価系及び動物試験系を確立し、15報の治療薬候補に関する論文を発表したことである。さらにゲノム情報が不十分であった媾疫トリパノソーマのゲノムと遺伝子発現情報を解析し、今後の治療薬開発研究に用いる基礎的な情報を得たことである。
また社会的意義として、研究過程でトリパノソーマ症汚染国の発展途上国由来の薬用植物成分の抗トリパノソーマ活性を明らかにしたことで、発展途上国において自国の天然資源を用いたトリパノソーマ症治療薬開発の可能性を提示したことである。

Research Products

• [Int'l Joint Research] モンゴル獣医学研究所(モンゴル)
• [Int'l Joint Research] ノースウエスト大学(南アフリカ)
• [Int'l Joint Research] Institute of Veterinary Medicine/National University of Mongolia(モンゴル)
• [Int'l Joint Research] North-West University(南アフリカ)
• [Journal Article] Effect of vegetable oils on the experimental infection of mice with Trypanosoma congolense (2020)
  • Author(s): Kume Aiko、Suganuma Keisuke、Umemiya-Shirafuji Rika、Suzuki Hiroshi
  • Journal Title: Experimental Parasitology Volume: 210 Pages: 107845-107845
  • DOI: 10.1016/j.exppara.2020.107845
  • Peer Reviewed
• [Journal Article] Polyradiculoneuropathy in dourine-affected horses (2019)
  • Author(s): Mungun-Ochir Bayasgalan、Horiuchi Noriyuki、Altanchimeg Adilbish、Koyama Kenji、Suganuma Keisuke、Nyamdolgor Uranbileg、Watanabe Ken-ichi、Baatarjargal Purevdorj、Mizushima Daiki、Battur Banzragch、Yokoyama Naoaki、Battsetseg Badgar、Inoue Noboru、Kobayashi Yoshiyasu
  • Journal Title: Neuromuscular Disorders Volume: 29 Issue: 6 Pages: 437-443
  • DOI: 10.1016/j.nmd.2019.03.005
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Short- and long-term effects of orally administered azithromycin on Trypanosoma brucei brucei-infected mice (2019)
  • Author(s): Molefe Nthatisi I.、Musinguzi Peter S.、Kondoh Daisuke、Watanabe Kenichi、Thekisoe Oriel M.M.、Xuan Xuenan、Inoue Noboru、Suganuma Keisuke
  • Journal Title: Experimental Parasitology Volume: 199 Pages: 40-46
  • DOI: 10.1016/j.exppara.2019.02.018
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Flavonoids isolated from the flowers of Pulsatilla flavescens and their anti-piroplasm activity (2019)
  • Author(s): Ganchimeg Dorj、Batbold Badarch、Murata Toshihiro、Davaapurev Bekh-Ochir、Munkhjargal Tserendorj、Tuvshintulga Bumduuren、Suganuma Keisuke、Igarashi Ikuo、Buyankhishig Buyanmandakh、Sasaki Kenroh、Batsuren Dulamjav、Batkhuu Javzan
  • Journal Title: Journal of Natural Medicines Volume: 07 Issue: 3 Pages: 1-8
  • DOI: 10.1007/s11418-019-01294-8
  • NAID: 40021912748
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Acylated Lignans Isolated from Brachanthemum gobicum and Their Trypanocidal Activity (2019)
  • Author(s): Odonbayar B, Murata T, Suganuma K, Ishikawa Y, Buyankhishig B, Batkhuu J, Sasaki K.
  • Journal Title: J. Nat. Prod Volume: 82 Issue: 4 Pages: 774-784
  • DOI: 10.1021/acs.jnatprod.8b00670
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Draft Genome Sequence of Trypanosoma equiperdum Strain IVM-t1 (2019)
  • Author(s): Davaasuren Batdorj、Yamagishi Junya、Mizushima Daiki、Narantsatsral Sandagdorj、Otgonsuren Davaajav、Myagmarsuren Punsantsogvoo、Battsetseg Badgar、Battur Banzragch、Inoue Noboru、Suganuma Keisuke
  • Journal Title: Microbiology Resource Announcements Volume: 8 Issue: 9 Pages: 1-3
  • DOI: 10.1128/mra.01119-18
  • Peer Reviewed
• [Journal Article] Utilization of crude and recombinant ELISAs for serodiagnosis of camel trypanosomosis in Sudan (2019)
  • Author(s): Mossaad Ehab、Salim Bashir、Suganuma Keisuke、Hassan Mohammed A.、Davaasuren Batdorj、Elamin Elgailani A.、Bakhiet Amel O.、Satti Rawan A.、Xuan Xuenan、Musinguzi Simon Peter、Inoue Noboru
  • Journal Title: Veterinary Parasitology: Regional Studies and Reports Volume: 16 Pages: 100278-100278
  • DOI: 10.1016/j.vprsr.2019.100278
  • Peer Reviewed
• [Journal Article] The utility of an rTeGM6-4r-based immunochromatographic test for the serological diagnosis of non-tsetse-transmitted equine trypanosomosis in rural areas of Mongolia (2018)
  • Author(s): Mizushima Daiki、Amgalanbaatar Tovuu、Davaasuren Batdorj、Molefe Nthatisi Innocentia、Battur Banzragch、Battsetseg Badgar、Inoue Noboru、Yokoyama Naoaki、Suganuma Keisuke
  • Journal Title: Parasitology Research Volume: 117 Issue: 9 Pages: 2913-2919
  • DOI: 10.1007/s00436-018-5982-8
  • Peer Reviewed
• [Journal Article] Metal nanoparticles restrict the growth of protozoan parasites (2018)
  • Author(s): Adeyemi Oluyomi Stephen、Molefe Nthatisi Innocentia、Awakan Oluwakemi Josephine、Nwonuma Charles Obiora、Alejolowo Omokolade Oluwaseyi、Olaolu Tomilola、Maimako Rotdelmwa Filibus、Suganuma Keisuke、Han Yongmei、Kato Kentaro
  • Journal Title: Artificial Cells, Nanomedicine, and Biotechnology Volume: 46 Issue: sup3 Pages: 86-94
  • DOI: 10.1080/21691401.2018.1489267
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lanostane triterpenoids from Fomitopsis officinalis and their trypanocidal activity (2018)
  • Author(s): Naranmandakh Shinen、Murata Toshihiro、Odonbayar Batsukh、Suganuma Keisuke、Batkhuu Javzan、Sasaki Kenroh
  • Journal Title: Journal of Natural Medicines Volume: 72 Issue: 2 Pages: 523-529
  • DOI: 10.1007/s11418-018-1182-1
  • NAID: 40021511419
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 特集 人に死を招く動物-人･昆虫･寄生虫 ツェツェバエ-アフリカ睡眠病(アフリカトリパノソーマ症) (2017)
  • Author(s): 菅沼啓輔、北潔
  • Journal Title: 公衆衛生 Volume: 81 Issue: 2 Pages: 129-134
  • DOI: 10.11477/mf.1401208608
  • ISSN: 0368-5187, 1882-1170
  • Year and Date: 2017-02-15
• [Journal Article] Oral administration of azithromycin ameliorates trypanosomosis in Trypanosoma congolense-infected mice (2017)
  • Author(s): Molefe Nthatisi Innocentia、Yamasaki Shino、Macalanda Adrian Miki C.、Suganuma Keisuke、Watanabe Kenichi、Xuan Xuenan、Inoue Noboru
  • Journal Title: Parasitology Research Volume: 116 Issue: 9 Pages: 2407-2415
  • DOI: 10.1007/s00436-017-5542-7
  • NAID: 120006411413
  • Peer Reviewed
• [Journal Article] Flavonoid and Galloyl Glycosides Isolated from Saxifraga spinulosa and Their Antioxidative and Inhibitory Activities against Species That Cause Piroplasmosis (2017)
  • Author(s): Badral Duger、Odonbayar Batsukh、Murata Toshihiro、Munkhjargal Tserendorj、Tuvshintulga Bumduuren、Igarashi Ikuo、Suganuma Keisuke、Inoue Noboru、Brantner Adelheid H.、Odontuya Gendaram、Sasaki Kenroh、Batkhuu Javzan
  • Journal Title: Journal of Natural Products Volume: 80 Issue: 9 Pages: 2416-2423
  • DOI: 10.1021/acs.jnatprod.7b00142
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] An ATP-Based Luciferase Viability Assay for Animal African Trypanosomes Using a 96-Well Plate (2017)
  • Author(s): Suganuma Keisuke、Molefe Nthatisi Innocentia、Inoue Noboru
  • Journal Title: Methods in Molecular Biology Volume: Cell Viability Assay Pages: 89-95
  • DOI: 10.1007/978-1-4939-6960-9_8
  • ISBN: 9781493969593, 9781493969609
• [Journal Article] The establishment of in vitro culture and drug screening systems for a newly isolated strain of Trypanosoma equiperdum (2017)
  • Author(s): Suganuma Keisuke、Yamasaki Shino、Nthatisi Innocentia Molefe、Peter Simon Musinguzi、Batdorj Davaasuren、Ehab Mossaad、Sandagdorj Narantsatsral、Banzragch Battur、Badgar Battsetseg、Inoue Noboru
  • Journal Title: International Journal for Parasitology: Drugs and Drug Resistance Volume: 7 Issue: 2 Pages: 200-205
  • DOI: 10.1016/j.ijpddr.2017.04.002
  • NAID: 120006390982
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification and characterization of guanosine 5′-monophosphate reductase of Trypanosoma congolense as a drug target (2017)
  • Author(s): Sarwono Albertus Eka Yudistira、Suganuma Keisuke、Mitsuhashi Shinya、Okada Tadashi、Musinguzi Simon Peter、Shigetomi Kengo、Inoue Noboru、Ubukata Makoto
  • Journal Title: Parasitology International Volume: 66 Issue: 5 Pages: 537-544
  • DOI: 10.1016/j.parint.2017.03.006
  • Peer Reviewed
• [Journal Article] Trypanocidal activity, cytotoxicity and histone modifications induced by malformin A1 isolated from the marine-derived fungus Aspergillus tubingensis IFM 63452. (2016)
  • Author(s): Notarte KI, Nakao Y, Yaguchi T, Bungihan M, Suganuma K, dela Cruz TE.
  • Journal Title: Mycosphere Volume: 8 Issue: 1 Pages: 111-120
  • DOI: 10.5943/mycosphere/8/1/10
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Trypanocidal Activity of 2,5-Diphenyloxazoles Isolated from the Roots of Oxytropis lanata (2016)
  • Author(s): Orkhon Banzragchgarav, Toshihiro Murata, Gendaram Odontuya, Buyanmandakh Buyankhishig, Keisuke Suganuma, Bekh-Ochir Davaapurev, Noboru Inoue, Javzan Batkhuu, and Kenroh Sasaki
  • Journal Title: Journal of Natural Products Volume: 79 Issue: 11 Pages: 2933-2940
  • DOI: 10.1021/acs.jnatprod.6b00778
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mycophenolic acid and its derivatives as potential chemotherapeutic agents targeting inosine monophosphate dehydrogenase in Trypanosoma congolense. (2016)
  • Author(s): Suganuma K, Sarwono AEY, Mitshuhashi S, Jakalski M, Okada T, Nthatisi M, Yamagishi J, Ubukata M, Inoue N
  • Journal Title: Antimicrobial Agents Chemother. Volume: 60 Issue: 7 Pages: 4391-4393
  • DOI: 10.1128/aac.02816-15
  • NAID: 120006390948
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The isolation, cultivation and molecular characterization of a new Trypanosoma equiperdum strain in Mongolia. (2016)
  • Author(s): Suganuma K, Narantsatsral S, Battur B, Yamasaki S, Otgonsuren D, Musinguzi SP, Davaasuren B, Battsetseg B, Inoue N.
  • Journal Title: Parasit Vectors Volume: 9 Issue: 1 Pages: 481-481
  • DOI: 10.1186/s13071-016-1755-3
  • NAID: 120006390952
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Dourine (Trypanosoma equiperdum infection in equidae) control campaign in Mongolia (2019)
  • Author(s): Keisuke Suganuma, Sandagdorj Narantsatsral, Batdorj Davaasuren, Daiki Mizushima, Badgar Batsetseg, Banzragch Battur, Noboru Inoue
  • Organizer: Conference on the cooperation and collaboration on prevention and control of animal disease
  • Int'l Joint Research / Invited
• [Presentation] Epidemiological studies on equine trypanosomosis in donkeys in Sudan (2019)
  • Author(s): Afraa Elata, Keisuke Suganuma, Ehab Mossaad, Rawan Satti, Xuenan Xuan, Noboru Inoue
  • Organizer: 第9回家畜感染症学会学術集会
• [Presentation] Draft Genome Sequence of Trypanosoma equiperdum IVM-t1 Strain (2019)
  • Author(s): Batdorj Davaasuren, Junya Yamagishi, Daiki Mizushima, Sandagdorj Narantsatsral, Davaajav Otgonsuren, Punsantsogvoo Myagmarsuren, Badgar Battsetseg, Banzragch Battur, Noboru Inoue, Keisuke Suganuma
  • Organizer: 4th international confernce on non-tsetse transmitted animal trypanosomes and trypanosomoses
  • Int'l Joint Research
• [Presentation] The screening of trypanocidal compounds extracted from Mongolian herbal plants against T. equiperdum Mongolian strains (2019)
  • Author(s): Keisuke Suganuma, Toshihiro Murata, Narantsatsral Sandagdorj, Orkhon Banzragchgarav, Batsukh Odonbayar, Davaasuren Batdorj, Javzan Batkhuu, Kenroh Sasaki, Banzragch Battur, Badgar Battsetseg, Noboru Inoue
  • Organizer: 4th international confernce on non-tsetse transmitted animal trypanosomes and trypanosomoses
  • Int'l Joint Research
• [Presentation] Trypanosome and trypanosomosis researches in Mongolia (2018)
  • Author(s): Suganuma K, Narantsatsral S, Batsetseg B, Battur B, Watanabe K, Kobayashi Y, Yokoyama N, Inoue N
  • Organizer: The 161st meeting of the Japanese Society of Veterinary Science
  • Invited
• [Presentation] Diagnostics and countermeasures of dourine in Mongolia (2018)
  • Author(s): Narantsatsral Sandagdorj, Davkharbayar Batbold, Amgalanbaatar Tovuu, Keisuke Suganuma, Daiki Mizushima, Zoljargal Myagmar, Baatarjargal Purevdorj, Soyolmaa Gurdorj, Nyamdolgor Uranbileg, Mungun-Ochir Bayasgalan, Altanchimeg Adilbish, Noboru Inoue, Battsetseg Badgar, Battur Banzragch
  • Organizer: The 3rd International Conference on Non-Tsetse Transmitted Animal Trypanosomosis
• [Presentation] Treatment efficiency of combination therapy using diminazene aceturate and quinapyramine sulfate for a dourine horse (2018)
  • Author(s): Batbold Davkharbayar, Batdorj Davaasuren, Sandagdorj Narantsatsral, Banzragch Battur, Myagmarsuren Pusangtsogvoo, Badgar Batsetseg, Daiki Mizushima, Noboru Inoue, Keisuke Suganuma
  • Organizer: The 3rd International Conference on Non-Tsetse Transmitted Animal Trypanosomosis
• [Presentation] モンゴルにおける媾疫トリパノソーマの研究 (2017)
  • Author(s): 菅沼啓輔、Naransatsral S, Battsetseg B, Battur B, 井上昇
  • Organizer: 第86回寄生虫学会大会 生態・疫学談話会
  • Invited
• [Presentation] Establishment of in vitro drug sensitivity assay against T. equiperdum Mongolian strains and the screening of trypanocidal compounds extracted from Mongolian herbal plants. (2017)
  • Author(s): 3.Suganuma K, Murata T, Molefe NI, Narantsatsral S, Orkhon B, Batsukh O, Davaasuren B, Mizushima B, Javzan B, Sasaki K, Battur B, Battsetseg B, Inoue N
  • Organizer: Achievements and current level of veterinary-biological sciences
  • Int'l Joint Research / Invited
• [Presentation] Characterisation of newly isolated and culture adapted Trypanosoma equiperdum. (2017)
  • Author(s): Suganuma K, Narantsatsral S, Battur B, Battsetseg B, Inoue N.
  • Organizer: 2nd International Conference on Non Tsetse Transmitted Animal Trypanosomosis
  • Int'l Joint Research / Invited
• [Presentation] 1.Dourine and T. equiperdum in Mongolia ~update from 2016: epidemiological study and in vitro culture of newly isolated T. equiperdum~ (2017)
  • Author(s): Keisuke Suganuma, Narantsatsral Sandagdorj, Davaasuren Batdorj, Daiki Mizushima, Nthatisi Innocentia Molefe, Battur Banzragch, Otgonsuren Davaajav, Battsetseg Badgar, Noboru Inoue
  • Organizer: The 3nd Annual Meeting of the OIE Non-Tsetse Transmitted Animal Trypanosomosis Network
  • Int'l Joint Research
• [Presentation] 新たに分離した媾疫トリパノソーマ株のキネトプラスト解析 (2017)
  • Author(s): 菅沼 啓輔, 近藤 大輔, Molefe Ntatisi Innocentia, Davaasuren Batdorj, 水島 大貴、井上 昇
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] 媾疫トリパノソーマ（Trypanosoma equiperdum）の分離と新規原虫株樹立 (2016)
  • Author(s): 菅沼 啓輔, Sandagdorj Narantsatsral, Banzragch Battur, 山﨑 詩乃, Davaajav Otgonsuren, Musinguzi Simon Peter, Batdorj Davaasuren Badgar Battsetseg, 井上 昇
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 日本大学（藤沢市、神奈川県）
  • Year and Date: 2016-09-06
• [Presentation] 媾疫（こうえき）トリパノソーマ （Trypanosoma equiperdum） 新規リファレンス株の樹立 (2016)
  • Author(s): 菅沼 啓輔, Sandagdorj Narantsatsral, Banzragch Battur, 山﨑 詩乃, Davaajav Otgonsuren, Musinguzi Simon Peter, Batdorj Davaasuren Badgar Battsetseg, 井上 昇
  • Organizer: 第24回分子寄生虫学ワークショップ・第14回分子寄生虫・マラリアフォ―ラム
  • Place of Presentation: 帯広畜産大学（帯広市、北海道）
  • Year and Date: 2016-08-21
• [Remarks] 帯広畜産大学原虫病研究センター
  • URL: https://www.obihiro.ac.jp/facility/protozoa/
• [Remarks] 帯広畜産大学 原虫病研究センター ホームページ
  • URL: http://www.obihiro.ac.jp/~protozoa/index.html