ArticleThe Journal of biological chemistry2016
Metabolic Cooperation of Glucose and Glutamine Is Essential for the Lytic Cycle of Obligate Intracellular Parasite Toxoplasma gondii.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49 citing papers in PubMed, 76 citations in OpenAlex.
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- RNA triphosphatase-mediated mRNA capping is essential for maintaining transcript homeostasis and the survival of Toxoplasma gondii.Nature communications · 2025Article
- Metabolic crosstalk between the mitochondrion and the nucleus is essential for Toxoplasma gondii infection.Communications biology · 2025Article
- The apicoplast localized isocitrate dehydrogenase is needed forFrontiers in cellular and infection microbiology · 2025Article
- Adaptations and metabolic evolution of myzozoan protists across diverse lifestyles and environments.Microbiology and molecular biology reviews : MMBR · 2024Review
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- Multiple pathways for glucose phosphate transport and utilization support growth of Cryptosporidium parvum.Nature communications · 2024Article
- Mitochondrial dysfunction induced by bedaquiline as an anti-Toxoplasma alternative.Veterinary research · 2023Article
- Gene expression profile of HCT-8 cells following single or co-infections with Cryptosporidium parvum and bovine coronavirus.Scientific reports · 2023Article
- Metabolic changes to host cells withbioRxiv : the preprint server for biology · 2023Article
- Multiple pathways for glucose phosphate transport and utilization support growth ofbioRxiv : the preprint server for biology · 2023Article
- An unconventional SNARE complex mediates exocytosis at the plasma membrane and vesicular fusion at the apical annuli in Toxoplasma gondii.PLoS pathogens · 2023Article
- The Toxoplasma micropore mediates endocytosis for selective nutrient salvage from host cell compartments.Nature communications · 2023Article
- Two apicoplast dwelling glycolytic enzymes provide key substrates for metabolic pathways in the apicoplast and are critical for Toxoplasma growth.PLoS pathogens · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toxoplasma gondii is a widespread protozoan parasite infecting nearly all warm-blooded organisms. Asexual reproduction of the parasite within its host cells is achieved by consecutive lytic cycles, which necessitates biogenesis of significant energy and biomass. Here we show that glucose and glutamine are the two major physiologically important nutrients used for the synthesis of macromolecules (ATP, nucleic acid, proteins, and lipids) in T. gondii, and either of them is sufficient to ensure the parasite survival. The parasite can counteract genetic ablation of its glucose transporter by increasing the flux of glutamine-derived carbon through the tricarboxylic acid cycle and by concurrently activating gluconeogenesis, which guarantee a continued biogenesis of ATP and biomass for host-cell invasion and parasite replication, respectively. In accord, a pharmacological inhibition of glutaminolysis or oxidative phosphorylation arrests the lytic cycle of the glycolysis-deficient mutant, which is primarily a consequence of impaired invasion due to depletion of ATP. Unexpectedly, however, intracellular parasites continue to proliferate, albeit slower, notwithstanding a simultaneous deprivation of glucose and glutamine. A growth defect in the glycolysis-impaired mutant is caused by a compromised synthesis of lipids, which cannot be counterbalanced by glutamine but can be restored by acetate. Consistently, supplementation of parasite cultures with exogenous acetate can amend the lytic cycle of the glucose transport mutant. Such plasticity in the parasite's carbon flux enables a growth-and-survival trade-off in assorted nutrient milieus, which may underlie the promiscuous survival of T. gondii tachyzoites in diverse host cells. Our results also indicate a convergence of parasite metabolism with cancer cells.
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