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

KAMIL M., Atmaca H. N., Unal S., KINA Ü. Y., Burak P., DEVECİ G., ...More

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol.66, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 66
  • Publication Date: 2022
  • Doi Number: 10.1128/aac.00269-22
  • Journal Name: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database, DIALNET
  • Keywords: malaria, Plasmodium yoelii, chloroquine, drug resistance, autophagy, drug resistance mechanisms, TRANSMEMBRANE PROTEIN PFCRT, PLASMODIUM-FALCIPARUM, MUTATIONS, QUININE, DEATH
  • Yıldız Technical University Affiliated: No

Abstract

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.