An Alternative Autophagy-Related Mechanism of Chloroquine Drug Resistance in the Malaria Parasite

Antimicrob Agents Chemother. 2022 Dec 20;66(12):e0026922. doi: 10.1128/aac.00269-22. Epub 2022 Nov 7.


We generated highly chloroquine (CQ)-resistant (ResCQ) Plasmodium yoelii parasites by stepwise exposure to increasing concentrations of CQ and CQ-sensitive parasites (SenCQ) by parallel mock treatments. No mutations in genes that are associated with drug resistance were detected in ResCQ clones. Autophagy-related genes were highly upregulated in SenCQ compared to ResCQ parasites during CQ treatment. This indicates that CQ resistance can be developed in the malaria parasite by the inhibition of autophagy as an alternative drug resistance mechanism.

Keywords: Plasmodium yoelii; autophagy; chloroquine; drug resistance; drug resistance mechanisms; malaria.

Publication types

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

MeSH terms

  • Antimalarials* / pharmacology
  • Antimalarials* / therapeutic use
  • Chloroquine* / pharmacology
  • Chloroquine* / therapeutic use
  • Drug Resistance* / genetics
  • Humans
  • Malaria / drug therapy
  • Malaria / parasitology
  • Plasmodium yoelii* / drug effects
  • Plasmodium yoelii* / genetics
  • Protozoan Proteins* / genetics


  • Antimalarials
  • Chloroquine
  • Protozoan Proteins