IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-17781-6.html
   My bibliography  Save this article

The natural function of the malaria parasite’s chloroquine resistance transporter

Author

Listed:
  • Sarah H. Shafik

    (The Australian National University)

  • Simon A. Cobbold

    (University of Melbourne)

  • Kawthar Barkat

    (The Australian National University)

  • Sashika N. Richards

    (The Australian National University)

  • Nicole S. Lancaster

    (The Australian National University)

  • Manuel Llinás

    (The Pennsylvania State University)

  • Simon J. Hogg

    (The Australian National University)

  • Robert L. Summers

    (The Australian National University)

  • Malcolm J. McConville

    (University of Melbourne)

  • Rowena E. Martin

    (The Australian National University)

Abstract

The Plasmodium falciparum chloroquine resistance transporter (PfCRT) is a key contributor to multidrug resistance and is also essential for the survival of the malaria parasite, yet its natural function remains unresolved. We identify host-derived peptides of 4-11 residues, varying in both charge and composition, as the substrates of PfCRT in vitro and in situ, and show that PfCRT does not mediate the non-specific transport of other metabolites and/or ions. We find that drug-resistance-conferring mutations reduce both the peptide transport capacity and substrate range of PfCRT, explaining the impaired fitness of drug-resistant parasites. Our results indicate that PfCRT transports peptides from the lumen of the parasite’s digestive vacuole to the cytosol, thereby providing a source of amino acids for parasite metabolism and preventing osmotic stress of this organelle. The resolution of PfCRT’s native substrates will aid the development of drugs that target PfCRT and/or restore the efficacy of existing antimalarials.

Suggested Citation

  • Sarah H. Shafik & Simon A. Cobbold & Kawthar Barkat & Sashika N. Richards & Nicole S. Lancaster & Manuel Llinás & Simon J. Hogg & Robert L. Summers & Malcolm J. McConville & Rowena E. Martin, 2020. "The natural function of the malaria parasite’s chloroquine resistance transporter," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17781-6
    DOI: 10.1038/s41467-020-17781-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-17781-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-17781-6?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
    ---><---

    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:11:y:2020:i:1:d:10.1038_s41467-020-17781-6. 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.