ArticlePLoS pathogens2020
Toxoplasma gondii requires its plant-like heme biosynthesis pathway for infection.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- 5-Aminolevulinic acid fluorescence in brain non-neoplastic lesions: a systematic review and case series.Neurosurgical review · 2022Pooled it
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- Integrated Proteomic Screening Reveals Heme Enzyme Depletion Induces Cyst-like Vacuole Formation inInternational journal of molecular sciences · 2026Article
- Is heme metabolism a promising drug target in Toxoplasma gondii?PLoS pathogens · 2026Article
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- A two-membrane gateway for monocarboxylates couples host glycolysis tobioRxiv : the preprint server for biology · 2026Article
- ZFT is the major iron and zinc transporter ineLife · 2026Article
- Oxadiargyl analogs as potent inhibitors ofRSC medicinal chemistry · 2026Article
- An apicoplast-localized GTPase is essential formSphere · 2026Article
- Transporters, an important but poorly studied area of Toxoplasma gondii.Parasites & vectors · 2026Review
- The phytochemical arbutin exerts potent anti-Toxoplasma effects through activation of cell-autonomous defense mechanisms while attenuating inflammation.PLoS neglected tropical diseases · 2025Article
- Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle.Nature communications · 2025Article
- TgGloL is an atypical glyoxalase/VOC domain-containing apicoplast protein that is important for the growth ofMolecular biology of the cell · 2025Article
- Iron-mediated post-transcriptional regulation in Toxoplasma gondii.PLoS pathogens · 2025Article
- The apicoplast localized isocitrate dehydrogenase is needed forFrontiers in cellular and infection microbiology · 2025Article
- Article
- A pyruvate transporter in the apicoplast of apicomplexan parasites.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Metabolic plasticity, essentiality and therapeutic potential of ribose-5-phosphate synthesis in Toxoplasma gondii.Nature communications · 2024Article
- Article
- Iron Stress Affects the Growth and Differentiation ofInternational journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Heme, an iron-containing organic ring, is essential for virtually all living organisms by serving as a prosthetic group in proteins that function in diverse cellular activities ranging from diatomic gas transport and sensing, to mitochondrial respiration, to detoxification. Cellular heme levels in microbial pathogens can be a composite of endogenous de novo synthesis or exogenous uptake of heme or heme synthesis intermediates. Intracellular pathogenic microbes switch routes for heme supply when heme availability fluctuates in their replicative environment throughout infection. Here, we show that Toxoplasma gondii, an obligate intracellular human pathogen, encodes a functional heme biosynthesis pathway. A chloroplast-derived organelle, termed apicoplast, is involved in heme production. Genetic and chemical manipulation revealed that de novo heme production is essential for T. gondii intracellular growth and pathogenesis. Surprisingly, the herbicide oxadiazon significantly impaired Toxoplasma growth, consistent with phylogenetic analyses that show T. gondii protoporphyrinogen oxidase is more closely related to plants than mammals. This inhibition can be enhanced by 15- to 25-fold with two oxadiazon derivatives, lending therapeutic proof that Toxoplasma heme biosynthesis is a druggable target. As T. gondii has been used to model other apicomplexan parasites, our study underscores the utility of targeting heme biosynthesis in other pathogenic apicomplexans, such as Plasmodium spp., Cystoisospora, Eimeria, Neospora, and Sarcocystis.
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