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Identification of drug resistant genes against partner drugs of ACT

Research Project

Project/Area Number 17H04071
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Parasitology (including sanitary zoology)
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Shiroh Iwanaga  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (20314510)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywordsマラリア / 薬剤耐性 / メフロキン
Outline of Final Research Achievements

Global spread of drug-resistant Plasmodium falciparum is a major obstacle to malaria treatment. Although the identification of drug resistance genes is crucial to efforts aimed at fighting resistant parasites, no effective approach has yet been developed. Here, we report genome-wide functional screening as a new approach to identify drug resistance genes in P. falciparum: genomic libraries of a drug-resistant strain are directly generated in drug-sensitive parasites and the drug resistance gene is then robustly identified from these libraries by drug screening. We successfully used this approach to identify multi-drug-resistant transporter 7, an ATP-binding cassette transporter, as a novel mefloquine resistance gene from a field-isolated parasite strain, thus demonstrating the practical utility of the method. Genome-wide functional screening will facilitate the identification of drug resistance genes and will contribute to the global fight against drug-resistant parasites.

Academic Significance and Societal Importance of the Research Achievements

マラリア治療にはアルテミシニンとパートナー薬剤(メフロキン・ピペラキン)による併用療法(ACT)が用いられる。しかし現在、パートナー薬剤に対する耐性が蔓延しており、耐性を回避するパートナー薬剤の選択がACTの成否の鍵となっている。最適なパートナー薬剤を選択するためには耐性原虫の蔓延状況を正確に把握する必要がある。しかしピペラキンとは異なりメフロキン耐性原虫の蔓延状況は未だ正確に把握されていない。これに対し本研究の成果はメフロキン耐性を監視する絶対的な分子マーカー(耐性遺伝子)を与える。これにより正確な疫学調査に基づく最適なパートナー薬剤の選択が可能となり、成功率の高いACTを提供できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (20 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (8 results) (of which Int'l Joint Research: 4 results,  Invited: 6 results)

  • [Int'l Joint Research] タイ国立遺伝子生命工学研究センター(タイ)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Entomological Assessment of the Status and Risk of Mosquito-borne Arboviral Transmission in Ghana2020

    • Author(s)
      Amoa-Bosompem M, Kobayashi D, Murota K, Faizah A N、Itokawa K、Fujita R、Osei Joseph H N、Agbosu E、Pratt D、Kimura S、Kwofie Kofi D、Ohashi M、Bonney Joseph H. K、Dadzie S、Sasaki T、Ohta N、Isawa H、Sawabe K、Iwanaga S
    • Journal Title

      Viruses

      Volume: 12 Issue: 2 Pages: 147-147

    • DOI

      10.3390/v12020147

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Female‐specific gene regulation in malaria parasites by an AP2‐family transcription factor2019

    • Author(s)
      Yuda Masao、Kaneko Izumi、Iwanaga Shiroh、Murata Yuho、Kato Tomomi
    • Journal Title

      Molecular Microbiology

      Volume: 113 Issue: 1 Pages: 40-51

    • DOI

      10.1111/mmi.14334

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CXCR4 regulates Plasmodium development in mouse and human hepatocytes2019

    • Author(s)
      Bando Hironori、Pradipta Ariel、Iwanaga Shiroh、Okamoto Toru、Okuzaki Daisuke、Tanaka Shun、Vega-Rodr?guez Joel、Lee Youngae、Ma Ji Su、Sakaguchi Naoya、Soga Akira、Fukumoto Shinya、Sasai Miwa、Matsuura Yoshiharu、Yuda Masao、Jacobs-Lorena Marcelo、Yamamoto Masahiro
    • Journal Title

      Journal of Experimental Medicine

      Volume: 216 Issue: 8 Pages: 1733-1748

    • DOI

      10.1084/jem.20182227

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Antimalarial activity of vitamin D3 (VD3) does not result from VD3-induced antimicrobial agents including nitric oxide or cathelicidin2019

    • Author(s)
      Yamamoto Kiichi、Takahashi Kentaro、Ato Manabu、Iwanaga Shiroh、Ohta Nobuo
    • Journal Title

      Experimental Parasitology

      Volume: 18 Pages: 30464-30468

    • DOI

      10.1016/j.exppara.2019.03.005

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral activity of the antimalarial endoperoxide 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) against Leishmania donovani complex2019

    • Author(s)
      Kwofie Kofi Dadzie、Sato Kai、Sanjoba Chizu、Hino Akina、Shimogawara Rieko、Amoa-Bosompem Michael、Ayi Irene、Boakye Daniel A.、Anang Abraham K.、Chang Kyung-Soo、Ohashi Mitsuko、Kim Hye-Sook、Ohta Nobuo、Matsumoto Yoshitsugu、Iwanaga Shiroh
    • Journal Title

      PLOS Neglected Tropical Diseases

      Volume: 13 Issue: 3 Pages: 7235-7235

    • DOI

      10.1371/journal.pntd.0007235

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Establishment of a quantitative and qualitative analysis and isolation method for tetracyclic iridoids from Morinda lucida Bentham leaves2019

    • Author(s)
      Ohta Tomoe、Tilkanont Tanatorn、Ayertey Frederick、Nakagawa Mina、Tung Nguyen Huu、Bolah Peter、Blagogee Heron、Appiah Alfred Ampomah、Ocloo Augustine、Ohashi Mitsuko、Tanoue Kensuke、Yamaguchi Yasuchika、Ohta Nobuo、Yamaoka Shoji、Iwanaga Shiro、Uto Takuhiro、Shoyama Yukihiro
    • Journal Title

      Journal of Pharmaceutical and Biomedical Analysis

      Volume: 164 Pages: 475-480

    • DOI

      10.1016/j.jpba.2018.10.044

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Molecular characterisation of the NDM-1-encoding plasmid p2189-NDM in an Escherichia coli ST410 clinical isolate from Ghana2018

    • Author(s)
      Ayibieke Alafate、Sato Wakana、Mahazu Samiratu、Prah Isaac、Addow-Thompson John、Ohashi Mitsuko、Suzuki Toshihiko、Iwanaga Shiroh、Ablordey Anthony、Saito Ryoichi
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 12 Pages: 0209623-0209623

    • DOI

      10.1371/journal.pone.0209623

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CRISPR/Cas9 system in Plasmodium falciparum using the centromere plasmid2018

    • Author(s)
      Payungwoung Tongchai、Shinzawa Naoaki、Hino Akina、Nishi Tubasa、Murata Yuho、Yuda Masao、Iwanaga Shiroh
    • Journal Title

      Parasitology International

      Volume: 67 Issue: 5 Pages: 605-608

    • DOI

      10.1016/j.parint.2018.06.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insights into the mode of action of 1,2,6,7-tetraoxaspiro [7.11] nonadecane (N-89) against adult Schistosoma mansoni worms2018

    • Author(s)
      Blay Emmanuel Awusah、Kumagai Takashi、Yamabe Masafumi、Hino Akina、Shimogawara Rieko、Kim Hye-Sook、Sato Akira、Ichimura Koichiro、Ayi Irene、Iwanaga Shiroh、Ohta Nobuo
    • Journal Title

      Parasitology International

      Volume: 67 Issue: 4 Pages: 403-412

    • DOI

      10.1016/j.parint.2018.03.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors2017

    • Author(s)
      Saito Fumiji、Hirayasu Kouyuki、Satoh Takeshi、Wang Christian W.、Lusingu John、Arimori Takao、Shida Kyoko、Palacpac Nirianne Marie Q.、Itagaki Sawako、Iwanaga Shiroh、Takashima Eizo、Tsuboi Takafumi、Kohyama Masako、Suenaga Tadahiro、Colonna Marco、Takagi Junichi、Lavstsen Thomas、Horii Toshihiro、Arase Hisashi
    • Journal Title

      Nature.

      Volume: 552 Issue: 7683 Pages: 101-105

    • DOI

      10.1038/nature24994

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A potent malaria vaccine based on adenovirus with dual modifications at Hexon and pVII2017

    • Author(s)
      Shiratsuchi Takayuki、Rai Urvashi、Kaneko Izumi、Zhang Min、Iwanaga Shiroh、Yuda Masao、Tsuji Moriya
    • Journal Title

      Vaccine

      Volume: 35 Issue: 50 Pages: 6990-7000

    • DOI

      10.1016/j.vaccine.2017.10.066

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] マラリア原虫有性ステージ分化におけるRNA結合型ジンクフィンガータンパク質ファミリーの解析2019

    • Author(s)
      平山 泰士、新澤 直明、油田 正夫、岩永 史朗
    • Organizer
      第79回 日本寄生虫学会東日本支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Female-specific gene regulation in malaria parasite by an AP2-family transcription factor.2019

    • Author(s)
      Shiroh Iwanaga
    • Organizer
      The 18th Awaji International Forum on Infectiopn and Immunity
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Transcriptional Regulation of Plasmodium parasites: Functional Analysis of AP2 Transcription Factors2018

    • Author(s)
      Shiroh Iwanaga
    • Organizer
      91th, Japanese society of biochemistry
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Transcriptional regulation mechanism of Plasmodium parasites.2018

    • Author(s)
      Shiroh Iwanaga, Masao Yuda
    • Organizer
      ICOPA 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Transcriptional Regulation of Plasmodium parasites: Functional Analysis of AP2 Transcription Factors2018

    • Author(s)
      Shiroh Iwanaga
    • Organizer
      Noguchi Hideyo Memorial Museum Symposium on Infectious Disease and Immunity
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Novel method for identification of drug resistance genes from P. falciparum using the artificial chromosome technology.2018

    • Author(s)
      Shiroh Iwanaga
    • Organizer
      SYMPOSIUM TO COMMEMORATE THE 90TH ANNIVERSARY OF DR. HIDEYO NOGUCHI’S ARRIVAL IN GHANA
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Drug resistance in malaria2017

    • Author(s)
      岩永史朗
    • Organizer
      第86回日本寄生虫学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Novel method for ideftification of drug resistace genes from P. falciparum using the artificial chromosome technology2017

    • Author(s)
      岩永史朗
    • Organizer
      The 90th Anniversary symposium of Dr. Hideyo Noguchi’s arrival in Ghana
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2017-04-28   Modified: 2021-02-19  

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