ArticlePLoS pathogens2013
Toxoplasma gondii relies on both host and parasite isoprenoids and can be rendered sensitive to atorvastatin.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed, 88 citations in OpenAlex.
- The mevalonate and methylerythritol phosphate pathways as therapeutic targets in protozoan parasites: from moonlighting enzymes to metabolic plasticity.Cell communication and signaling : CCS · 2026Review
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- Evolutionary remodeling of ubiquinone biosynthesis in Toxoplasma gondii reveals an essential bi-functional monooxygenase.Nature communications · 2026Article
- The early human interferon gamma response to Toxoplasma gondii is driven by Vγ9Vδ2 T-cell sensing of host phosphoantigens and subsequent NK-cell activation.PLoS pathogens · 2025Article
- Host-Derived Geranylgeraniol Shields Intraerythrocytic Stages of Malaria Parasites from Fosmidomycin.Research square · 2025Article
- Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle.Nature communications · 2025Article
- The apicoplast localized isocitrate dehydrogenase is needed forFrontiers in cellular and infection microbiology · 2025Article
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- TheeLife · 2024Article
- Beyond the MEP Pathway: A novel kinase required for prenol utilization by malaria parasites.PLoS pathogens · 2024Article
- Transcriptomic and metabolomic analyses reveal the essential nature of Rab1B in Toxoplasma gondii.Parasites & vectors · 2023Article
- Functional screening revealsmBio · 2023Article
- Antiplasmodial, Trypanocidal, and GenotoxicityPharmaceuticals (Basel, Switzerland) · 2023Article
- Prenyl Transferases Regulate Secretory Protein Sorting and Parasite Morphology inInternational journal of molecular sciences · 2023Article
- The Biomedical Importance of the Missing Pathway for Farnesol and Geranylgeraniol Salvage.Molecules (Basel, Switzerland) · 2022Review
- Parasite powerhouse: A review of the Toxoplasma gondii mitochondrion.The Journal of eukaryotic microbiology · 2022Review
- Article
- The ferredoxin redox system - an essential electron distributing hub in the apicoplast of Apicomplexa.Trends in parasitology · 2022Review
- Modulation of autophagy as a therapeutic strategy forFrontiers in cellular and infection microbiology · 2022Review
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4 authors at 1 institution in 1 country.
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Abstract
Intracellular pathogens have complex metabolic interactions with their host cells to ensure a steady supply of energy and anabolic building blocks for rapid growth. Here we use the obligate intracellular parasite Toxoplasma gondii to probe this interaction for isoprenoids, abundant lipidic compounds essential to many cellular processes including signaling, trafficking, energy metabolism, and protein translation. Synthesis of precursors for isoprenoids in Apicomplexa occurs in the apicoplast and is essential. To synthesize longer isoprenoids from these precursors, T. gondii expresses a bifunctional farnesyl diphosphate/geranylgeranyl diphosphate synthase (TgFPPS). In this work we construct and characterize T. gondii null mutants for this enzyme. Surprisingly, these mutants have only a mild growth phenotype and an isoprenoid composition similar to wild type parasites. However, when extracellular, the loss of the enzyme becomes phenotypically apparent. This strongly suggests that intracellular parasite salvage FPP and/or geranylgeranyl diphosphate (GGPP) from the host. We test this hypothesis using inhibitors of host cell isoprenoid synthesis. Mammals use the mevalonate pathway, which is susceptible to statins. We document strong synergy between statin treatment and pharmacological or genetic interference with the parasite isoprenoid pathway. Mice can be cured with atorvastatin (Lipitor) from a lethal infection with the TgFPPs mutant. We propose a double-hit strategy combining inhibitors of host and parasite pathways as a novel therapeutic approach against Apicomplexan parasites.
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