ArticleProceedings of the National Academy of Sciences of the United States of America2007
Discovery of parasite virulence genes reveals a unique regulator of chromosome condensation 1 ortholog critical for efficient nuclear trafficking.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- An Unusual U2AF2 Inhibits Splicing and Attenuates the Virulence of the Human Protozoan ParasiteFrontiers in cellular and infection microbiology · 2022Article
- Tandem mass tag (TMT)-based proteomic analysis of Cryptosporidium andersoni oocysts before and after excystation.Parasites & vectors · 2021Article
- Genomic Signatures of Coevolution between Nonmodel Mammals and Parasitic Roundworms.Molecular biology and evolution · 2021Article
- A Toxoplasma gondii patatin-like phospholipase contributes to host cell invasion.PLoS pathogens · 2020Article
- The chromatin bound proteome of the human malaria parasite.Microbial genomics · 2020Article
- A latent ability to persist: differentiation in Toxoplasma gondii.Cellular and molecular life sciences : CMLS · 2018Review
- mRNA export in the apicomplexan parasite Toxoplasma gondii: emerging divergent components of a crucial pathway.Parasites & vectors · 2018Review
- Patatin-like phospholipases in microbial infections with emerging roles in fatty acid metabolism and immune regulation by Apicomplexa.Molecular microbiology · 2018Review
- Developmental change in translation initiation alters the localization of a common microbial protein necessary for Toxoplasma chronic infection.Molecular microbiology · 2016Article
- Article
- DNA repair mechanisms and Toxoplasma gondii infection.Archives of microbiology · 2014Review
- Disruption of the expression of a non-coding RNA significantly impairs cellular differentiation in Toxoplasma gondii.International journal of molecular sciences · 2012Article
- Discovery of a novel Toxoplasma gondii conoid-associated protein important for parasite resistance to reactive nitrogen intermediates.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Cytoskeleton assembly in Toxoplasma gondii cell division.International review of cell and molecular biology · 2012Review
- Examination of a virulence mutant uncovers the ribosome biogenesis regulatory protein of Toxoplasma gondii.The Journal of parasitology · 2011Article
- A Toxoplasma gondii mutant highlights the importance of translational regulation in the apicoplast during animal infection.Molecular microbiology · 2011Article
- A transmembrane domain containing pellicle protein of Toxoplasma gondii enhances virulence and invasion after extracellular stress.Molecular and biochemical parasitology · 2011Article
- Parasite-mediated upregulation of NK cell-derived gamma interferon protects against severe highly pathogenic H5N1 influenza virus infection.Journal of virology · 2011Article
- TgVTC2 is involved in polyphosphate accumulation in Toxoplasma gondii.Molecular and biochemical parasitology · 2011Article
- A systems biological view of intracellular pathogens.Immunological reviews · 2011Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Eukaryotic parasites are a leading cause of morbidity and mortality worldwide, yet little is known about the genetic basis of their virulence. Here, we present a forward genetic screen to study pathogenesis in the protozoan parasite Toxoplasma gondii. By using modified signature-tagged mutagenesis, the growth of 6,300 T. gondii insertional mutants was compared in cell culture and murine infection to identify genes required specifically in vivo. One of the 39 avirulent mutants is disrupted in a divergent ortholog of the regulator of chromosome condensation 1 (RCC1), which is critical for nuclear trafficking in model systems. Although this RCC1 mutant grows similar to wild type in standard tissue culture conditions, it is growth-impaired under nutrient limitation. Genetic complementation of mutant parasites with the T. gondii RCC1 gene fully restores both virulence in mice and growth under low-nutrient conditions. Further analysis shows that there is a significant defect in nuclear trafficking in the RCC1 mutant. These findings suggest that the rate of nuclear transport is a critical factor affecting growth in low-nutrient conditions in vivo and in vitro. Additionally, we observed that although RCC1 proteins are highly conserved in organisms from humans to yeast, no protozoan parasite encodes a characteristic RCC1. This protein divergence may represent a unique mechanism of nucleocytoplasmic transport. This study illustrates the power of this forward genetics approach to identify atypical virulence mechanisms.
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