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 Pathog. 2016 Aug 4;12(8):e1005765. doi: 10.1371/journal.ppat.1005765. eCollection 2016 Aug.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apicoplasts / enzymology*
  • Chromatography, Liquid
  • Fluorescent Antibody Technique
  • Gene Knockdown Techniques
  • Glycerol-3-Phosphate O-Acyltransferase / metabolism*
  • Lysophospholipids / biosynthesis
  • Mass Spectrometry
  • Microscopy, Electron, Transmission
  • Models, Molecular
  • Phospholipids / biosynthesis*
  • Phylogeny
  • Polymerase Chain Reaction
  • Protozoan Proteins / biosynthesis*
  • Protozoan Proteins / chemistry
  • Toxoplasma / metabolism*

Substances

  • Lysophospholipids
  • Phospholipids
  • Protozoan Proteins
  • Glycerol-3-Phosphate O-Acyltransferase
  • lysophosphatidic acid

Grants and funding

CYB gratefully acknowledges grants from Agence Nationale pour la recherche (ANR RPDOC Apicolipid and Parafrap labex ANR-11-LABX-0024, France), ATIP-Avenir (CNRS-Inserm France), Fondation Innovation en Infectiologie (Finovi Apicolipid), Université Grenoble Alpes (AGIR Apicolipid) for their support to this work and to SA, MJS (ANR), YYB (ANR, Finovi), DD (Atip-Avenir). GIM acknowledges a Program Grant from the National Health and Medical Research Council (Australia) and a Discovery Grant from Australian Research Council. MJM is an NHMRC Principal Research Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.