Apicoplast-Localized Lysophosphatidic Acid Precursor Assembly Is Required for Bulk Phospholipid Synthesis in Toxoplasma gondii and Relies on an Algal/Plant-Like Glycerol 3-Phosphate Acyltransferase

PLoS Pathogens

Souad Amiar¹  Melanie J. Shears¹  Eric Maréchal¹  Geoffrey I. McFadden²  David Dubois³  Damien L. Callahan⁴  Cyrille Y. Botté⁴  Marie-France Cesbron-Delauw⁵  Malcolm J. McConville⁶  Giel G. van Dooren⁶  James I. MacRae⁷  Yoshiki Yamaryo-Botté⁸ 

[1] ApicoLipid group, Institute for Advanced Biosciences UMR5309, CNRS, Université Grenoble Alpes, INSERM, Grenoble, France;BNI group, TIMC-IMAG UMR5525 CNRS, Université Grenoble Alpes, Grenoble, France;Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences, Deakin University, Burwood, Victoria, Australia;Department of Biochemistry and Molecular Biology, Bio21 Molecular Science & Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia;Research School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia;School of BioSciences, University of Melbourne, Melbourne, Victoria, Australia;The Francis Crick Institute, The Ridgeway, Mill Hill, London, United Kingdom;Unité de recherche (UMR) 5168, CNRS, CEA, INRA, Université Grenoble Alpes, Grenoble, France

关键词: Fatty acids;    Toxoplasma gondii;    Biosynthesis;    Lipids;    Parasite replication;    Lipid analysis;    Glycerol;    Phospholipids;   

DOI  :  10.1371/journal.ppat.1005765

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY