title: Mitochondrial metabolism of glucose and glutamine is required for intracellular growth of Toxoplasma gondii.
abstract: Toxoplasma gondii proliferates within host cell vacuoles where the parasite relies on host carbon and nutrients for replication. To assess how T. gondii utilizes these resources, we mapped the carbon metabolism pathways in intracellular and egressed parasite stages. We determined that intracellular T. gondii stages actively catabolize host glucose via a canonical, oxidative tricarboxylic acid (TCA) cycle, a mitochondrial pathway in which organic molecules are broken down to generate energy. These stages also catabolize glutamine via the TCA cycle and an unanticipated γ-aminobutyric acid (GABA) shunt, which generates GABA and additional molecules that enter the TCA cycle. Chemically inhibiting the TCA cycle completely prevents intracellular parasite replication. Parasites lacking the GABA shunt exhibit attenuated growth and are unable to sustain motility under nutrient-limited conditions, suggesting that GABA functions as a short-term energy reserve. Thus, T. gondii tachyzoites have metabolic flexibility that likely allows the parasite to infect diverse cell types.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: James I
authors.initials: JI
authors.lastname: MacRae
authors.forename: Lilach
authors.initials: L
authors.lastname: Sheiner
authors.forename: Amsha
authors.initials: A
authors.lastname: Nahid
authors.forename: Christopher
authors.initials: C
authors.lastname: Tonkin
authors.forename: Boris
authors.initials: B
authors.lastname: Striepen
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: McConville
mesh_terms: D000154:Aconitate Hydratase / Q000037:antagonists & inhibitors; D000818:Animals; D002952:Citric Acid Cycle / Q000187:drug effects; D005227:Fatty Acids / Q000096:biosynthesis; D005463:Fluoroacetates / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006790:Host-Parasite Interactions; D008928:Mitochondria / Q000378:metabolism*; D014122:Toxoplasma / Q000254:growth & development* / Q000378:metabolism*; D014124:Toxoplasmosis, Animal / Q000378:metabolism / Q000469:parasitology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D005463:Fluoroacetates; D005973:Glutamine; D005680:gamma-Aminobutyric Acid; C014815:fluoroacetic acid; D000154:Aconitate Hydratase; D005947:Glucose