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

doi:10.1128/AAC.02256-17

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 journal › Article › peer-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 language	English
Article number	e02256-17
Journal	Antimicrobial Agents and Chemotherapy
Volume	62
Issue number	5
DOIs	https://doi.org/10.1128/AAC.02256-17
Publication status	Published - May 2018
Externally published	Yes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1128/AAC.02256-17

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

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.",

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AU - Roberts, David J.

AU - Wellems, Thomas E.

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

Abstract

Bibliographical note

Keywords

UN SDGs

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