IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms8485.html
   My bibliography  Save this article

Caenorhabditis elegans is a useful model for anthelmintic discovery

Author

Listed:
  • Andrew R. Burns

    (The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto)

  • Genna M. Luciani

    (The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
    University of Toronto)

  • Gabriel Musso

    (Brigham and Women’s Hospital, Harvard Medical School, and Harvard Stem Cell Institute
    Harvard Medical School)

  • Rachel Bagg

    (The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto)

  • May Yeo

    (The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto)

  • Yuqian Zhang

    (The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto)

  • Luckshika Rajendran

    (The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto)

  • John Glavin

    (The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto)

  • Robert Hunter

    (The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto)

  • Elizabeth Redman

    (Faculty of Veterinary Medicine, University of Calgary)

  • Susan Stasiuk

    (Faculty of Veterinary Medicine, University of Calgary)

  • Michael Schertzberg

    (The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto)

  • G. Angus McQuibban

    (University of Toronto, 1 King's College Circle)

  • Conor R. Caffrey

    (University of California)

  • Sean R. Cutler

    (Center for Plant Cell Biology, University of California)

  • Mike Tyers

    (Institute for Research in Immunology and Cancer, University of Montreal)

  • Guri Giaever

    (University of British Columbia)

  • Corey Nislow

    (University of British Columbia)

  • Andy G. Fraser

    (The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
    University of Toronto)

  • Calum A. MacRae

    (Brigham and Women’s Hospital, Harvard Medical School, and Harvard Stem Cell Institute
    Harvard Medical School)

  • John Gilleard

    (Faculty of Veterinary Medicine, University of Calgary)

  • Peter J. Roy

    (The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
    University of Toronto
    University of Toronto)

Abstract

Parasitic nematodes infect one quarter of the world’s population and impact all humans through widespread infection of crops and livestock. Resistance to current anthelmintics has prompted the search for new drugs. Traditional screens that rely on parasitic worms are costly and labour intensive and target-based approaches have failed to yield novel anthelmintics. Here, we present our screen of 67,012 compounds to identify those that kill the non-parasitic nematode Caenorhabditis elegans. We then rescreen our hits in two parasitic nematode species and two vertebrate models (HEK293 cells and zebrafish), and identify 30 structurally distinct anthelmintic lead molecules. Genetic screens of 19 million C. elegans mutants reveal those nematicides for which the generation of resistance is and is not likely. We identify the target of one lead with nematode specificity and nanomolar potency as complex II of the electron transport chain. This work establishes C. elegans as an effective and cost-efficient model system for anthelmintic discovery.

Suggested Citation

  • Andrew R. Burns & Genna M. Luciani & Gabriel Musso & Rachel Bagg & May Yeo & Yuqian Zhang & Luckshika Rajendran & John Glavin & Robert Hunter & Elizabeth Redman & Susan Stasiuk & Michael Schertzberg &, 2015. "Caenorhabditis elegans is a useful model for anthelmintic discovery," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8485
    DOI: 10.1038/ncomms8485
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms8485
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms8485?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Nicola Sasanelli & Alena Konrat & Varvara Migunova & Ion Toderas & Elena Iurcu-Straistaru & Stefan Rusu & Alexei Bivol & Cristina Andoni & Pasqua Veronico, 2021. "Review on Control Methods against Plant Parasitic Nematodes Applied in Southern Member States (C Zone) of the European Union," Agriculture, MDPI, vol. 11(7), pages 1-19, June.
    2. Muntasir Kamal & Jessica Knox & Robert I. Horne & Om Shanker Tiwari & Andrew R. Burns & Duhyun Han & Davide Levy & Dana Laor Bar-Yosef & Ehud Gazit & Michele Vendruscolo & Peter J. Roy, 2024. "A rapid in vivo pipeline to identify small molecule inhibitors of amyloid aggregation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Brandon M. Murareanu & Noelle V. Antao & Winnie Zhao & Aurore Dubuffet & Hicham El Alaoui & Jessica Knox & Damian C. Ekiert & Gira Bhabha & Peter J. Roy & Aaron W. Reinke, 2022. "High-throughput small molecule screen identifies inhibitors of microsporidia invasion and proliferation in C. elegans," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. Taylor Davie & Xènia Serrat & Lea Imhof & Jamie Snider & Igor Štagljar & Jennifer Keiser & Hiroyuki Hirano & Nobumoto Watanabe & Hiroyuki Osada & Andrew G. Fraser, 2024. "Identification of a family of species-selective complex I inhibitors as potential anthelmintics," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Jessica Knox & Andrew R. Burns & Brittany Cooke & Savina R. Cammalleri & Megan Kitner & Justin Ching & Jack M. P. Castelli & Emily Puumala & Jamie Snider & Emily Koury & J. B. Collins & Salma Geissah , 2024. "Cyprocide selectively kills nematodes via cytochrome P450 bioactivation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8485. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.