Fig. 10: Effect of MSO and PPT on Pf and Pv clinical isolates and ART-resistant PfCam3.I^R539T strain.

a Effect of MSO on in vitro growth of Pf (n = 7) and Pv (n = 6) clinical isolates in RPMI^-gln. b Effect of PPT on in vitro growth of Pf (n = 7) and Pv (n = 6) clinical isolates in RPMI^-gln. A growth assessment was carried out based on ³H-hypoxanthine uptake and verified by Giemsa-stained smears. c Effect of ART/DHA and MSO combination on the growth of ART-resistant PfCam3.I^R539T parasites in RSA were performed with RPMI^-gln medium. The percentage of growth inhibition of ART/DHA and MSO combination treatment was determined at 96 h with respect to ART/DHA-treated parasites. The percentage of growth inhibition of MSO treatment alone was determined at 96 h with respect to untreated parasites. d Effect of ART/DHA and PPT combination on the growth of ART-resistant PfCam3.I^R539T parasites in RSA were performed with RPMI^-gln medium. The percentage of growth inhibition of ART/DHA and PPT combination treatment was determined at 96 h with respect to ART/DHA-treated parasites. The percentage of growth inhibition of PPT treatment alone was determined at 96 h with respect to untreated parasites. Growth assessment was carried out based on ³H-hypoxanthine uptake and verified by Giemsa-stained smears and flow cytometry. (mean ± SD; **P < 0.01, ***P < 0.001, Two-way ANOVA) n = 3 independent experiments. e Model depicting the distinct evolution of Plasmodium GS and its significance in P. falciparum. Lack of feedback inhibition by amino acids and absence of adenylylation in Plasmodium GS are represented. Blue arrows highlight the requirement of GS in supporting Pf asparagine-rich proteome and the role of glutamine as a reservoir of nitrogen source in ART-resistance. FV- food vacuole; Mito - mitochondrion; RBC - red blood cell. The model was created with BioRender.com.