Evidence map›Paper›PMID 18780736›Full record

ArticleGenetics2008

Secondary mutations correct fitness defects in Toxoplasma gondii with dinitroaniline resistance mutations.

Christopher Ma, Johnson Tran, Catherine Li, Lakshmi Ganesan, David Wood, Naomi Morrissette

Abstract read
In one paragraph

Article in Genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
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

17 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Auranofin Resistance inFrontiers in cellular and infection microbiology · 2021
    Article
  7. Drug Resistance inFrontiers in microbiology · 2018
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
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

6 authors.

Christopher MaDepartment of Molecular Biology and Biochemistry, University of California, Irvine, California 92697-3900, USA.
Johnson Tran
Catherine Li
Lakshmi Ganesan
David Wood
Naomi Morrissette

Funding

Mechanisms of Dinitroaniline Action, Selectivity and ResistanceR01AI067981 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI MORRISSETTE, NAOMI S · 2006 to 2010
$1.7M
Dinitroaniline Specificity for TubulinK22AI055790 · NIAID · UNIVERSITY OF CALIFORNIA IRVINE · PI MORRISSETTE, NAOMI S · 2004 to 2005
$268k
NIAID NIH HHS AI055790NIAID NIH HHS AI067981NIAID NIH HHS K22 AI055790NIAID NIH HHS R01 AI067981
6 · The paper itself

Abstract

Dinitroanilines (oryzalin, trifluralin, ethafluralin) disrupt microtubules in protozoa but not in vertebrate cells, causing selective death of intracellular Toxoplasma gondii parasites without affecting host cells. Parasites containing alpha1-tubulin point mutations are dinitroaniline resistant but show increased rates of aberrant replication relative to wild-type parasites. T. gondii parasites bearing the F52Y mutation were previously demonstrated to spontaneously acquire two intragenic mutations that decrease both resistance levels and replication defects. Parasites bearing the G142S mutation are largely dependent on oryzalin for viable growth in culture. We isolated 46 T. gondii lines that have suppressed microtubule defects associated with the G142S or the F52Y mutations by acquiring secondary mutations. These compensatory mutations were alpha1-tubulin pseudorevertants or extragenic suppressors (the majority alter the beta1-tubulin gene). Many secondary mutations were located in tubulin domains that suggest that they function by destabilizing microtubules. Most strikingly, we identified seven novel mutations that localize to an eight-amino-acid insert that stabilizes the alpha1-tubulin M loop, including one (P364R) that acts as a compensatory mutation in both F52Y and G142S lines. These lines have reduced dinitroaniline resistance but most perform better than parental lines in competition assays, indicating that there is a trade-off between resistance and replication fitness.

Indexed as

MutationAniline CompoundsAnimalsDinitrobenzenesDrug ResistanceFluorescent Antibody TechniqueModels, MolecularProtein Structure, TertiarySulfanilamidesToxoplasmaTrifluralinTubulinTubulin ModulatorsAniline CompoundsDinitrobenzenesethafluralinoryzalinSulfanilamidesTrifluralinTubulinTubulin Modulators

Identifiers

PMID18780736
PMCPMC2567385

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.