Figure 7
Mechanism of KIC5 mutant sensitivity to artemisinin due to the putative activity of the KIC5 protein. In the isogenic wild-type NF54 clone, KIC5 expression at 6 hpi leads to the gene’s activity in chromosome segregation, chromatin condensation, and DNA repair during ring stage, a critical period of artemisinin resistance in P. falciparum. KIC5 activity leads to wild-type expression pattern of stress response mechanisms under artemisinin exposure, leading to wild-type artemisinin sensitive phenotype. In the KIC5 mutant, however, dysregulation of KIC5 expression from 6 to 24 hpi leads to a lack of KIC5 protein activity during ring stage. Temporal changes to KIC5 activity led to altered expression of genes linked to artemisinin stress response, including various nuclear and mitochondrial pathways. Under artemisinin exposure, altered expression patterns lead to abnormal artemisinin response and increased sensitivity. Created with BioRender.com.
