Evidence map›Paper›PMID 27481247›Full record

ArticleInfection and immunity2016

Pyrimidine Pathway-Dependent and -Independent Functions of the Toxoplasma gondii Mitochondrial Dihydroorotate Dehydrogenase.

Miryam Andrea Hortua Triana, Daniela Cajiao Herrera, Barbara H Zimmermann, Barbara A Fox, David J Bzik

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.2field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. Genetic analysis of pyrimidine biosynthetic enzymes inbioRxiv : the preprint server for biology · 2025
    Article
  4. Review
  5. Article
  6. FromiScience · 2024
    Article
  7. Article
  8. Animal venoms: a novel source of anti-Frontiers in pharmacology · 2023
    Review
  9. Parasite powerhouse: A review of the Toxoplasma gondii mitochondrion.The Journal of eukaryotic microbiology · 2022
    Review
  10. Biochemical Studies of Mitochondrial Malate: Quinone Oxidoreductase fromInternational journal of molecular sciences · 2021
    Article
  11. Article
  12. Frontiers in microbiology · 2019
    Article
  13. Article
  14. Article
  15. Pyrimidine metabolism in schistosomes: A comparison with other parasites and the search for potential chemotherapeutic targets.Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology · 2017
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Miryam Andrea Hortua TrianaDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Daniela Cajiao HerreraDepartamento de Ciencias Biológicas, Universidad de los Andes, Bogotá, Colombia.
Barbara H ZimmermannDepartamento de Ciencias Biológicas, Universidad de los Andes, Bogotá, Colombia.
Barbara A FoxDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
David J BzikDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA david.j.bzik@dartmouth.edu.
Dartmouth College · USUniversidad de Los Andes · CO

Funding

T GONDII--PYRIMIDINE SYNTHESIS AS A CHEMOTHERAPY TARGETR01AI041930 · NIAID · DARTMOUTH COLLEGE · PI BZIK, DAVID J · 1997 to 2013
$4.2M
NIAID NIH HHS R01 AI041930
6 · The paper itself

Abstract

Dihydroorotate dehydrogenase (DHODH) mediates the fourth step of de novo pyrimidine biosynthesis and is a proven drug target for inducing immunosuppression in therapy of human disease as well as a rapidly emerging drug target for treatment of malaria. In Toxoplasma gondii, disruption of the first, fifth, or sixth step of de novo pyrimidine biosynthesis induced uracil auxotrophy. However, previous attempts to generate uracil auxotrophy by genetically deleting the mitochondrion-associated DHODH of T. gondii (TgDHODH) failed. To further address the essentiality of TgDHODH, mutant gene alleles deficient in TgDHODH activity were designed to ablate the enzyme activity. Replacement of the endogenous DHODH gene with catalytically deficient DHODH gene alleles induced uracil auxotrophy. Catalytically deficient TgDHODH localized to the mitochondria, and parasites retained mitochondrial membrane potential. These results show that TgDHODH is essential for the synthesis of pyrimidines and suggest that TgDHODH is required for a second essential function independent of its role in pyrimidine biosynthesis.

Indexed as

Biosynthetic PathwaysDihydroorotate DehydrogenaseFibroblastsGene Knockout TechniquesHumansMitochondriaOxidoreductases Acting on CH-CH Group DonorsPyrimidinesToxoplasmaToxoplasmosisUracilDihydroorotate DehydrogenaseOxidoreductases Acting on CH-CH Group DonorsPyrimidinesUracil

Identifiers

PMID27481247
PMCPMC5038078
OpenAlexW2477545241

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.