Kelch Mutations in Plasmodium falciparum Protein K13 Do Not Modulate Dormancy after Artemisinin Exposure and Sorbitol Selection In Vitro

Kimberly F. Breglio, Rifat S. Rahman, Juliana M. Sá, David J. Roberts, Thomas E. Wellems*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Some Kelch mutations of the Plasmodium falciparum K13 protein confer increased survival to dihydroartemisinin (DHA)-treated ring-stage parasites. Here, we asked if K13 mutations affect a dormancy phenotype allowing parasites to survive DHA exposure and then sorbitol selection. Although recrudescence from dormancy differed between two distinct parasite lines, it was similar for isogenic lines carrying single-site substitutions in K13. Therefore, K13 mutations do not alter the DHA-sorbitol combined dormancy phenotype; rather, traits from other loci likely determine this phenotype.

Original languageEnglish
Article numbere02256-17
JournalAntimicrobial Agents and Chemotherapy
Volume62
Issue number5
DOIs
Publication statusPublished - May 2018
Externally publishedYes

Bibliographical note

Funding Information:
We thank Judith Straimer and David Fidock for providing the edited 967 parasite clones, and Katja Simon, Craig J. Thomas, and Rick Fairhurst for discussions. This work was supported by the NIH Oxford Scholars Program and by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. We declare no conflicts of interest.

Publisher Copyright:
Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords

  • Drug resistance
  • Malaria
  • Recrudescence

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