Artemisinin-based combination therapies (ACTs) have significantly reduced worldwide malaria burden and deaths, but the malaria parasites have become resistant to Artemisinins. Earlier studies have proposed dysregulation of proteostasis in endoplasmic reticulum (ER) as well as in cytoplasm for artemisinin resistance.
We investigated regulation of various stress responses underlying the mechanisms involved in artemisinin resistance.We have experimentally demonstrated that artemisinin and its derivatives induce parasite UPR which in turn upregulates Autophagy.We have also shown that one of the parasite Autophagy like protein PfATG18 participates in food vacuole (FV) fission and is trafficked to the parasite FV via hemoglobin uptake pathway which is also implicated in artemisinin resistance. Besides these non-canonical functions it is also involved in the parasite autophagy.
Schematic diagram of various roles of PfATG18
Agrawal. P., et. al. Autophagy-related protein PfATG18 participates in food vacuole dynamics and autophagy-like pathway in Plasmodium falciparum. Mol Microbiol. 2019.10.1111/mmi.14441.
Our studies thus have given leads to explore participation of various stress responses in artemisinin resistance.
