The intracellular parasite Toxoplasma gondii depends on the synthesis of long‐chain and very long‐chain unsaturated fatty acids not supplied by the host cell

• DOI: 10.1111/mmi.13010
• Publication Date: 2015-04-01T14:21:23Z
• Authors: Srinivasan Ramakr...; Melissa D. Docampo; James I. MacRae; Julie E. Ralton; Thusitha Rupasinghe; Malcolm J. McConv...; Boris Striepen
• Keywords: Apicoplast; Fatty acid synthesis; De novo synthesis; Intracellular parasite; Cerulenin

Apicomplexa are parasitic protozoa that cause important human diseases including malaria, cryptosporidiosis and toxoplasmosis. The replication of these parasites within their target host cell is dependent on both salvage as well de novo synthesis fatty acids. In Toxoplasma gondii, acid via the apicoplast-localized FASII essential for pathogenesis, while role two other biosynthetic complexes remains unclear. Here, we demonstrate ER-localized elongation (ELO) parasite growth. Conditional knockdown nonredundant hydroxyacyl-CoA dehydratase enoyl-CoA reductase enzymes in ELO pathway severely repressed intracellular (13) C-glucose C-acetate labeling comprehensive lipidomic analyses mutants showed a selective defect unsaturated long very long-chain acids (LCFAs VLCFAs) depletion phosphatidylinositol phosphatidylethanolamine species containing LCFAs VLCFAs. This requirement was bypassed by supplementing media with specific acids, indicating active but inefficient import Our experiments highlight gap between needs availability has to close using dedicated modification pathway.