ArticleInfection and immunity2010
Avirulent uracil auxotrophs based on disruption of orotidine-5'-monophosphate decarboxylase elicit protective immunity to Toxoplasma gondii.
Article in Infection and immunity, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 81 citations in OpenAlex.
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- Anti-Toxoplasma activity of NBMPR is mediated through the inhibition of nucleoside and nucleobase transporters.Parasitology research · 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
- From pathogen to cure: exploring the antitumor potential of Toxoplasma gondii.Infectious agents and cancer · 2025Review
- Toxoplasma gondii C2 Domain Protein Deletion Mutant as a Promising Vaccine Against Toxoplasmosis in Mice.Microbial biotechnology · 2025Article
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- Toxoplasma WH3 Δrop18 acts as a live attenuated vaccine against acute and chronic toxoplasmosis.NPJ vaccines · 2024Article
- Toxoplasma gondii-Derived Exosomes: A Potential Immunostimulant and Delivery System for Tumor Immunotherapy Superior to Toxoplasma gondii.International journal of nanomedicine · 2024Review
- Role of 6-phosphogluconate dehydrogenase enzyme 1 in growth and virulence of Toxoplasma gondii and development of attenuated live vaccine.Microbial biotechnology · 2023Article
- Loss in the Antibacterial Ability of a PyrR Gene Regulating Pyrimidine Biosynthesis after Using CRISPR/Cas9-Mediated Knockout for Metabolic Engineering inMicroorganisms · 2023Article
- A live attenuated RHΔompdcΔuprt mutant of Toxoplasma gondii induces strong protective immunity against toxoplasmosis in mice and cats.Infectious diseases of poverty · 2023Article
- Pyrimidine salvage inFrontiers in cellular and infection microbiology · 2023Article
- A novel enemy of cancer: recent investigations into protozoan anti-tumor properties.Frontiers in cellular and infection microbiology · 2023Review
- New Nucleic Base-Tethered Trithiolato-Bridged Dinuclear Ruthenium(II)-Arene Compounds: Synthesis and Antiparasitic Activity.Molecules (Basel, Switzerland) · 2022Article
- Attenuated Toxoplasma gondii enhances the antitumor efficacy of anti-PD1 antibody by altering the tumor microenvironment in a pancreatic cancer mouse model.Journal of cancer research and clinical oncology · 2022Article
- Deletion ofBiomedicines · 2022Article
- Review
- A uracil auxotroph Toxoplasma gondii exerting immunomodulation to inhibit breast cancer growth and metastasis.Parasites & vectors · 2021Article
- Genetic mapping reveals Nfkbid as a central regulator of humoral immunity to Toxoplasma gondii.PLoS pathogens · 2021Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
The orotidine-5'-monophosphate decarboxylase (OMPDC) gene, encoding the final enzyme of the de novo pyrimidine biosynthesis pathway, was deleted using Toxoplasma gondii KU80 knockouts to develop an avirulent nonreverting pyrimidine auxotroph strain. Additionally, to functionally address the role of the pyrimidine salvage pathway, the uridine phosphorylase (UP) salvage activity was knocked out and a double knockout of UP and OMPDC was also constructed. The nonreverting DeltaOMPDC, DeltaUP, and DeltaOMPDC DeltaUP knockout strains were evaluated for pyrimidine auxotrophy, for attenuation of virulence, and for their ability to elicit potent immunity to reinfection. The DeltaUP knockout strain was replication competent and virulent. In contrast, the DeltaOMPDC and DeltaOMPDC DeltaUP strains were uracil auxotrophs that rapidly lost their viability during pyrimidine starvation. Replication of the DeltaOMPDC strain but not the DeltaOMPDC DeltaUP strain was also partially rescued in vitro with uridine or cytidine supplementation. Compared to their hypervirulent parental type I strain, the DeltaOMPDC and DeltaOMPDC DeltaUP knockout strains exhibited extreme attenuation in murine virulence (approximately 8 logs). Genetic complementation of the DeltaOMPDC strain using a functional OMPDC allele restored normal replication and type I parental strain virulence phenotypes. A single immunization of mice with either the live critically attenuated DeltaOMPDC strain or the DeltaOMPDC DeltaUP knockout strain effectively induced potent protective immunity to lethal challenge infection. The avirulent nonreverting DeltaOMPDC and DeltaOMPDC DeltaUP strains provide new tools for the dissection of the host response to infection and are promising candidates for safe and effective Th1 vaccine platforms that can be easily genetically engineered.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.