Evidence map›Paper›PMID 25789621›Full record

ArticlePloS one2015

Yeast three-hybrid screen identifies TgBRADIN/GRA24 as a negative regulator of Toxoplasma gondii bradyzoite differentiation.

Anahi V Odell, Fanny Tran, Jenna E Foderaro, Séverine Poupart, Ravi Pathak, Nicholas J Westwood, Gary E Ward

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.2field-weighted citation impact, top 25% 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

8 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. mBio · 2020
    Article
  5. Article
  6. Article
  7. Article
  8. 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

7 authors at 2 institutions in 2 countries.

Anahi V OdellDepartment of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, United States of America.
Fanny TranSchool of Chemistry and Biomedical Sciences Research Complex, University of St. Andrews and EaStCHEM, St Andrews, Fife, Scotland, United Kingdom.
Jenna E FoderaroDepartment of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, United States of America.
Séverine PoupartSchool of Chemistry and Biomedical Sciences Research Complex, University of St. Andrews and EaStCHEM, St Andrews, Fife, Scotland, United Kingdom.
Ravi PathakSchool of Chemistry and Biomedical Sciences Research Complex, University of St. Andrews and EaStCHEM, St Andrews, Fife, Scotland, United Kingdom.
Nicholas J WestwoodSchool of Chemistry and Biomedical Sciences Research Complex, University of St. Andrews and EaStCHEM, St Andrews, Fife, Scotland, United Kingdom.
Gary E WardDepartment of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, United States of America.
University of St Andrews · GBUniversity of Vermont · US

Funding

Vermont Immunobioloigy/ Infectious Diseases CenterP20GM103496 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI BUDD, RALPH C · 2012 to 2015
$8.7M
Small Molecule Approaches to Studying T. gondii InvasionR01AI054961 · NIAID · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI WARD, GARY E · 2003 to 2014
$4.5M
Small Molecule Approaches to Studying T. gondi InvasionR56AI054961 · NIAID · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI WARD, GARY E · 2008 to 2008
$312k
NIAID NIH HHS AI054961NIAID NIH HHS R01 AI054961NIAID NIH HHS R56 AI054961NIGMS NIH HHS P20 GM103496
6 · The paper itself

Abstract

Differentiation of the protozoan parasite Toxoplasma gondii into its latent bradyzoite stage is a key event in the parasite's life cycle. Compound 2 is an imidazopyridine that was previously shown to inhibit the parasite lytic cycle, in part through inhibition of parasite cGMP-dependent protein kinase. We show here that Compound 2 can also enhance parasite differentiation, and we use yeast three-hybrid analysis to identify TgBRADIN/GRA24 as a parasite protein that interacts directly or indirectly with the compound. Disruption of the TgBRADIN/GRA24 gene leads to enhanced differentiation of the parasite, and the TgBRADIN/GRA24 knockout parasites show decreased susceptibility to the differentiation-enhancing effects of Compound 2. This study represents the first use of yeast three-hybrid analysis to study small-molecule mechanism of action in any pathogenic microorganism, and it identifies a previously unrecognized inhibitor of differentiation in T. gondii. A better understanding of the proteins and mechanisms regulating T. gondii differentiation will enable new approaches to preventing the establishment of chronic infection in this important human pathogen.

Indexed as

Two-Hybrid System Techniques3' Flanking RegionCell LineGene LibraryGenes, ProtozoanHumansImidazolesLife Cycle StagesMethotrexatePhenotypeProtein BindingProtozoan ProteinsPyrimidinesToxoplasma4-(7-((dimethylamino)methyl)-2-(4-fluorophenyl)imidazo(1,2-a)pyridin-3-yl)pyrimidin-2-amineImidazolesMethotrexateProtozoan ProteinsPyrimidines

Identifiers

PMID25789621
PMCPMC4366382
OpenAlexW2164720572

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.