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

Antimicrob Agents Chemother. 2018 Apr 26;62(5):e02256-17. doi: 10.1128/AAC.02256-17. Print 2018 May.

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.

Keywords: drug resistance; malaria; recrudescence.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / pharmacology*
  • Artemisinins / pharmacology*
  • Drug Resistance / genetics
  • Mutation / genetics
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics*
  • Polymorphism, Genetic / genetics
  • Sorbitol / pharmacology*

Substances

  • Antimalarials
  • Artemisinins
  • Sorbitol
  • artenimol