Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • NEWS AND VIEWS

Malaria parasites fine-tune mutations to resist drugs

Drug resistance in malaria parasites is mediated by mutations in a transporter protein. The transporter’s structure reveals the molecular basis of how key mutations bring about resistance to different drugs.
  1. Leann Tilley

    1. Leann Tilley is in the Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

    View author publications

    You can also search for this author in PubMed  Google Scholar

  2. Philip J. Rosenthal

    1. Philip J. Rosenthal is in the Department of Medicine, University of California, San Francisco, San Francisco, California 94143 USA.

    View author publications

    You can also search for this author in PubMed  Google Scholar

About half a million people, most of them children living in Africa, are killed each year by malaria1. Management of malaria, particularly that caused by the highly virulent protozoan parasite Plasmodium falciparum, is challenged by the emergence of resistance to antimalarial drugs2. Writing in Nature, Kim et al.3 report the structure and molecular properties of a key protein that facilitates resistance, the P. falciparum chloroquine-resistance transporter (PfCRT). The structure reveals the consequences of finely tuned mutations of the amino-acid residues that line a crucial central cavity in PfCRT. These mutated residues allow resistant parasites to transport certain antimalarial drugs away from their site of action — and the effect of the mutations is different for closely related drugs.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Nature 576, 217-219 (2019)

doi: https://doi.org/10.1038/d41586-019-03587-0

References

  1. World Health Organization. World Malaria Report 2018 (2018).

    Google Scholar 

  2. Haldar, K., Bhattacharjee, S. & Safeukui, I. Nature Rev. Microbiol. 16, 156–170 (2018).

    Google Scholar 

  3. Kim, L. et al. Nature 576, 315–320 (2019).

    Article  Google Scholar 

  4. Goldberg, D. E. Curr. Top. Microbiol. Immunol. 295, 275–291 (2005).

    Article  PubMed  Google Scholar 

  5. van der Pluijm, R. W. et al. Lancet Infect. Dis. 19, 952–961 (2019).

    Article  Google Scholar 

  6. Ross, L. S. et al. Nature Commun. 9, 3314 (2018).

    Article  Google Scholar 

  7. Fidock, D. A. et al. Mol. Cell 6, 861–871 (2000).

    Article  Google Scholar 

  8. Summers, R. L. et al. Proc. Natl Acad. Sci. USA 111, E1759–1767 (2014).

    Article  Google Scholar 

  9. Martin, R. E. & Kirk, K. Mol. Biol. Evol. 21, 1938–1949 (2004).

    Article  Google Scholar 

  10. Nogales, E. & Scheres, S. H. Mol. Cell 58, 677–689 (2015).

    Article  Google Scholar 

  11. Pelleau, S. et al. Proc. Natl Acad. Sci. USA 112, 11672–11677 (2015).

    Article  Google Scholar 

  12. Conrad, M. D. & Rosenthal, P. J. Lancet Infect. Dis. 19, e338–e351 (2019).

    Article  Google Scholar 

Download references

Subjects

Latest on:

Nature Careers

Jobs

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing

Search

Advanced search

Quick links