PLoS Pathog. 2016 Aug 4;12(8):e1005765. doi: 10.1371/journal.ppat.1005765. eCollection 2016.
Amiar S1,
MacRae JI2,3,
Callahan DL4,5,
Dubois D1,
van Dooren GG6,
Shears MJ1,5,
Cesbron-Delauw MF7,
Maréchal E8,
McConville MJ3,
McFadden GI5,
Yamaryo-Botté Y1,
Botté CY1.
Abstract
Most apicomplexan parasites possess a non-photosynthetic plastid (the apicoplast), which harbors enzymes for a number of metabolic pathways, including a prokaryotic type II fatty acid synthesis (FASII) pathway. In Toxoplasma gondii, the causative agent of toxoplasmosis, the FASII pathway is essential for parasite growth and infectivity. However, little is known about the fate of fatty acids synthesized by FASII. In this study, we have investigated the function of a plant-like glycerol 3-phosphate acyltransferase (TgATS1) that localizes to the T. gondii apicoplast. Knock-down of TgATS1 resulted in significantly reduced incorporation of FASII-synthesized fatty acids into phosphatidic acid and downstream phospholipids and a severe defect in intracellular parasite replication and survival. Lipidomic analysis demonstrated that lipid precursors are made in, and exported from, the apicoplast for de novo biosynthesis of bulk phospholipids. This study reveals that the apicoplast-located FASII and ATS1, which are primarily used to generate plastid galactolipids in plants and algae, instead generate bulk phospholipids for membrane biogenesis in T. gondii.
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