Fig 5.tif (966.66 kB)
Download file

The effect of MMV007839 on the metabolite profile of parasitised erythrocytes.

Download (966.66 kB)
figure
posted on 08.02.2017, 18:27 authored by Sanduni V. Hapuarachchi, Simon A. Cobbold, Sarah H. Shafik, Adelaide S. M. Dennis, Malcolm J. McConville, Rowena E. Martin, Kiaran Kirk, Adele M. Lehane

(A) Relative amounts of intracellular metabolites in MMV007839-treated parasitised erythrocytes (infected with the 3D7 strain) and untreated parasitised erythrocytes. The data shown are the mean log2 ratios of the level of each metabolite in the MMV007839-treated samples relative to its level in the untreated samples (+ MMV007839/- MMV007839), determined 1 h, 3 h and 6 h after the addition of MMV007839, obtained from three independent experiments. The concentration of MMV007839 used (6 μM) corresponds to approximately 20× the IC50 value for growth inhibition of 3D7 parasites. (B) The log2 ratios of metabolite levels in MMV007839-treated samples relative to those in untreated samples for all metabolites of known identity for which a statistically significant difference in abundance was observed between MMV007839-treated and untreated infected erythrocytes (see S1 Data for statistical analysis). The data shown are the mean + SEM from three independent experiments. GL3P, sn-glycerol-3-phosphate; Pyr, pyruvate; Lac, lactate; R5P, ribose-5-phosphate; AcCoA, acetyl coenzyme A; Gln, glutamine; VD, Val-Asp; PE, Pro-Glu; PVQ, Pro-Val-Gln; PDAV, Pro-Asp-Ala-Val; TNVK, Thr-Asn-Val-Lys; Oro, orotate; O5P, orotidine-5-phosphate; DC, deoxycytidine; GGPP, geranylgeranyl-pyrophosphate. (C) Relative amounts of metabolites in the extracellular medium in suspensions containing MMV007839-treated and untreated parasitised erythrocytes. The data shown are the mean log2 ratios (+ MMV007839/- MMV007839) + SEM from three independent experiments. There was a statistically significant difference in the concentrations of 3-phosphoglycerate and phosphoenolpyruvate in the extracellular medium between MMV007839-treated and untreated cell suspensions (see S1 Data). DHAP, glycerone phosphate; PEP, phosphoenolpyruvate; 3PG, 3-phosphoglycerate; Cit, citrate; αKG, 2-ketoglutarate; Mal, malate; Pip, pipecolate.

History