J Biol Chem. 2014 Jan 15. [Epub ahead of print]
Phosphatidylethanolamine synthesis in the parasite mitochondrion is required for efficient growth but dispensable for survival of Toxoplasma gondii.
Toxoplasma gondii is a highly prevalent obligate intracellular parasite of the phylum Apicomplexa that also includes other parasites of clinical/veterinary importance, such as Plasmodium, Cryptosporidium and Eimeria. Acute infection by Toxoplasma is hallmarked by rapid proliferation in its host cells, and requires synthesis of parasite membranes. Phosphatidylethanolamine (PtdEtn) is the second major phospholipid class in T. gondii. Here, we reveal that PtdEtn is produced in the parasite mitochondrion and parasitophorous vacuole by decarboxylation of phosphatidylserine (PtdSer), and in the endoplasmic reticulum by fusion of CDP-ethanolamine and diacylglycerol. PtdEtn in the mitochondrion is synthesized by a PtdSer decarboxylase (TgPSD1mt) of the type I class. TgPSD1mt harbors a targeting peptide at its N-terminus that is required for the mitochondrial localization but not for the catalytic activity. Ablation of TgPSD1mt expression caused up to 45% impairment in the parasite growth. The PtdEtn content of the parasite mutant was unaffected however, suggesting the presence of compensatory mechanisms. Indeed, metabolic labeling revealed an increased usage of ethanolamine for PtdEtn synthesis by the mutant strain, and depletion of nutrient exacerbated the growth defect (~56%), which was partially restored by ethanolamine. Further, the survival and residual growth of the TgPSD1mt mutant in the nutrient-depleted medium indicated additional routes of PtdEtn biogenesis such as acquisition of host-derived lipid. Collectively, these results demonstrate a metabolic cooperativity between the parasite organelles, which ensures a sustained lipid synthesis, survival and growth of T. gondii in varying nutritional milieus.
Host-pathogen interactions, Membrane biogenesis, Microbiology, Parasite metabolism, Parasitology, Phosphatidylethanolamine, phosphatidylserine decarboxylase
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