Early transcriptional response to chloroquine of the Plasmodium falciparum antioxidant defence in sensitive and resistant clones

Resistance to chloroquine (CQ) in Plasmodium falciparum has a major impact on malaria control worldwide. To gain insight into early parasite stress response, mRNA expression profiles were determined for a set of 10 antioxidant defence genes in synchronized CQ-sensitive (3D7) and CQ-resistant (Dd2) clones under transient IC50 CQ-exposure (Dd2, 200 nM; 3D7, 14 nM). Upon 2-h CQ challenge, the mRNA upregulation detected was greater in 3D7 (six genes overexpressed at 1/3 of the intraerythrocytic cycle) than in Dd2 clone (three genes responding), providing evidence of an early transcriptional response to CQ-induced oxidative stress which might underlie some of the parasite's metabolic adaptation to the drug.

Graphical abstractThe endogenous antioxidant defence system in Plasmodium falciparum is upregulated by chloroquine as a parasite's metabolic adaptation to the increased oxidative stress caused by the drug.Figure optionsDownload full-size imageDownload as PowerPoint slide