ArticleEukaryotic cell2011
Type II Toxoplasma gondii KU80 knockout strains enable functional analysis of genes required for cyst development and latent infection.
Article in Eukaryotic cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
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Who cites it
121 citing papers in PubMed.
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- Toxoplasma gondii as a drug for anti-tumor immunotherapy: mechanisms, challenges, and perspectives.Parasite (Paris, France) · 2026Review
- Cysteine-S-nitrosylation inhibits Rop5-mediated immune evasion inbioRxiv : the preprint server for biology · 2025Article
- The role of parasite-produced dopamine in Toxoplasma gondii-altered host behaviour.Nature communications · 2025Article
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- Motility-dependent processes inmSphere · 2025Article
- Paracrine rescue of MYR1-deficienteLife · 2024Article
- Motility-dependent processes inbioRxiv : the preprint server for biology · 2024Article
- A Toxoplasma gondii O-glycosyltransferase that modulates bradyzoite cyst wall rigidity is distinct from host homologues.Nature communications · 2024Article
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- ThemSphere · 2023Article
- A transcriptional network required for bradyzoite development in Toxoplasma gondii is dispensable for recrudescent disease.Nature communications · 2023Article
- Molecular Mechanisms of Persistence in Protozoan Parasites.Microorganisms · 2023Review
61 more citing papers are in PubMed but not listed here.
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9 authors.
Funding
Abstract
Type II Toxoplasma gondii KU80 knockouts (Δku80) deficient in nonhomologous end joining were developed to delete the dominant pathway mediating random integration of targeting episomes. Gene targeting frequency in the type II Δku80 Δhxgprt strain measured at the orotate (OPRT) and the uracil (UPRT) phosphoribosyltransferase loci was highly efficient. To assess the potential of the type II Δku80 Δhxgprt strain to examine gene function affecting cyst biology and latent stages of infection, we targeted the deletion of four parasite antigen genes (GRA4, GRA6, ROP7, and tgd057) that encode characterized CD8(+) T cell epitopes that elicit corresponding antigen-specific CD8(+) T cell populations associated with control of infection. Cyst development in these type II mutant strains was not found to be strictly dependent on antigen-specific CD8(+) T cell host responses. In contrast, a significant biological role was revealed for the dense granule proteins GRA4 and GRA6 in cyst development since brain tissue cyst burdens were drastically reduced specifically in mutant strains with GRA4 and/or GRA6 deleted. Complementation of the Δgra4 and Δgra6 mutant strains using a functional allele of the deleted GRA coding region placed under the control of the endogenous UPRT locus was found to significantly restore brain cyst burdens. These results reveal that GRA proteins play a functional role in establishing cyst burdens and latent infection. Collectively, our results suggest that a type II Δku80 Δhxgprt genetic background enables a higher-throughput functional analysis of the parasite genome to reveal fundamental aspects of parasite biology controlling virulence, pathogenesis, and transmission.
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