Fig. 10: Effect of griseofulvin on Pf parasites and model depicting the role of de novo heme in regulating FV integrity and Hz formation. | Nature Communications

Fig. 10: Effect of griseofulvin on Pf parasites and model depicting the role of de novo heme in regulating FV integrity and Hz formation.

From: Malaria parasite heme biosynthesis promotes and griseofulvin protects against cerebral malaria in mice

Fig. 10: Effect of griseofulvin on Pf parasites and model depicting the role of de novo heme in regulating FV integrity and Hz formation.The alternative text for this image may have been generated using AI.

a Effect of griseofuvin on Pf3D7 parasite growth. The data (mean ± SD; R square = 0.8623) represent three different experiments. Individual data points are shown with the light shaded color. b Incorporation of 14C-ALA into Pf3D7 parasite de novo heme. The radioactive counts represent three different experiments (mean ± SD; *P < 0.05, **P < 0.01, unpaired t-test; two-sided). Individual data points are shown as black circles. Phosphorimager and scanned images of TLC performed for 14C-ALA labeled parasite free heme are also shown. Full-length scans are provided in the Supplementary Fig. 7. c Pf3D7 parasite Hz. d Pf3D7 parasite free heme. The data represent three different experiments (mean ± SD; *P < 0.05, **P < 0.01, unpaired t-test; two-sided). For c and d, individual data points are shown as black circles. e Giemsa-stained images of Pf3D7 parasites treated with griseofulvin. ET and LT early and late trophozoites; ES and LS early and late schizonts. Images were captured using 100x objective. Scale bar = 5 μm. n = 3 independent experiments. f Assessment of parasite Hz, free heme and growth in Pf clinical isolates. The data represent two different experiments for each clinical isolate. Percentage of inhibition was calculated with respect to untreated DMSO control. Individual data points are shown. g De novo heme pathway of malaria parasite and Hz formation in the FV are represented. Solid arrows indicate the effect of de novo heme on V-type H+-ATPase, FV pH and OA synthesis affecting hemozoin formation. Dashed arrows represent the probable effects of de novo heme on Hb endocytosis, and protein and lipid trafficking. Gly glycine, Succ-coA succinyl coenzymeA, ALA δ-aminolevulinic acid, PBG prophobilinogen, URogenIII uroporphyrinogen III, CPogenIII coproporphyrinogen III, PPogenIII protoporphyrinogen III, PPIX protoporphyrin IX, ER endoplasmic reticulum. Source data are provided as a Source Data file.

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