ArticlePLoS pathogens2012
The polymorphic pseudokinase ROP5 controls virulence in Toxoplasma gondii by regulating the active kinase ROP18.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 177 citations in OpenAlex.
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- Discovery of potent anti-toxoplasmosis drugs from secondary metabolites in Citrus limon (lemon) leaves, supported in-silico study.Scientific reports · 2025Article
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- TBC9, an essential TBC-domain protein, regulates early vesicular transport and IMC formation in Toxoplasma gondii.Communications biology · 2024Article
- iNOS is necessary for GBP-mediated T. gondii clearance in murine macrophages via vacuole nitration and intravacuolar network collapse.Nature communications · 2024Article
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- Structural basis of Irgb6 inactivation by Toxoplasma gondii through the phosphorylation of switch I.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Toxoplasma protein export and effector function.Nature microbiology · 2024Review
- Early immune response toFrontiers in cellular and infection microbiology · 2024Article
- Genetic diversity of Toxoplasma gondii in South America: occurrence, immunity, and fate of infection.Parasites & vectors · 2023Review
- Histone variant H2B.Z acetylation is necessary for maintenance of Toxoplasma gondii biological fitness.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
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51 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Secretory polymorphic serine/threonine kinases control pathogenesis of Toxoplasma gondii in the mouse. Genetic studies show that the pseudokinase ROP5 is essential for acute virulence, but do not reveal its mechanism of action. Here we demonstrate that ROP5 controls virulence by blocking IFN-γ mediated clearance in activated macrophages. ROP5 was required for the catalytic activity of the active S/T kinase ROP18, which phosphorylates host immunity related GTPases (IRGs) and protects the parasite from clearance. ROP5 directly regulated activity of ROP18 in vitro, and both proteins were necessary to avoid IRG recruitment and clearance in macrophages. Clearance of both the Δrop5 and Δrop18 mutants was reversed in macrophages lacking Irgm3, which is required for IRG function, and the virulence defect was fully restored in Irgm3(-/-) mice. Our findings establish that the pseudokinase ROP5 controls the activity of ROP18, thereby blocking IRG mediated clearance in macrophages. Additionally, ROP5 has other functions that are also Irgm3 and IFN-γ dependent, indicting it plays a general role in governing virulence factors that block immunity.
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Registered trials
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