Spermidine Is The Main Polyamine Required By Intracellular Parasites For Survival Within Host Erythrocytes

AbstractIntracellular eukaryotic pathogens such asBabesiaandPlasmodium, the agents of human babesiosis and malaria, require salvage or de novo synthesis of several nutrients for survival in human erythrocytes. One such nutrient is putrescine, which is either transported from the host or synthesized from ornithine and serves as a precursor for the biosynthesis of two other polyamines: spermidine and spermine. However, the specific polyamines required by these parasites for survival and the molecular process they control remain unknown. We show in bothB. duncaniandP. falciparumthat spermidine is the main product of the polyamine biosynthesis machinery required for parasite survival. Simultaneous inhibition of spermidine synthesis from putrescine and catabolism from spermine results in cell death and parasite survival can only be rescued by spermidine. Finally, we demonstrate that spermidine’s essential function in these parasites is through regulation of protein translation via hypusination of the translation initiation factor eIF5A.