Evidence map›Paper›PMID 17881728›Full record

ArticleMolecular biology of the cell2007

Mutations in alpha-tubulin confer dinitroaniline resistance at a cost to microtubule function.

Christopher Ma, Catherine Li, Lakshmi Ganesan, Jean Oak, Susan Tsai, David Sept, Naomi S Morrissette

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

20 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Molecular Evolution of Tubulins in Diatoms.International journal of molecular sciences · 2022
    Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Drug Resistance inFrontiers in microbiology · 2018
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

7 authors at 2 institutions in 1 country.

Christopher MaDepartment of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA.
Catherine Li
Lakshmi Ganesan
Jean Oak
Susan Tsai
David Sept
Naomi S Morrissette
University of California, Irvine · USWashington University in St. Louis · US

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 AI-055790NIAID NIH HHS AI-067981NIAID NIH HHS K22 AI055790NIAID NIH HHS R01 AI067981
6 · The paper itself

Abstract

Protozoan microtubules are sensitive to disruption by dinitroanilines, compounds that kill intracellular Toxoplasma gondii parasites without affecting microtubules in vertebrate host cells. We previously isolated a number of resistant Toxoplasma lines that harbor mutations to the alpha1-tubulin gene. Some of the mutations are localized in or near the M and N loops, domains that coordinate lateral interactions between protofilaments. Other resistance mutations map to a computationally identified binding site beneath the N loop. Allelic replacement of wild-type alpha1-tubulin with the individual mutations is sufficient to confer dinitroaniline resistance. Some mutations seem to increase microtubule length, suggesting that they increase subunit affinity. All mutations are associated with replication defects that decrease parasite viability. When parasites bearing the N loop mutation Phe52Tyr are grown without dinitroaniline selection, they spontaneously acquired secondary mutations in the M loop (Ala273Val) or in an alpha-tubulin-specific insert that stabilizes the M loop (Asp367Val). Parasites with the double mutations have both reduced resistance and diminished incidence of replication defects, suggesting that the secondary mutations decrease protofilament affinity to increase parasite fitness.

Indexed as

Drug ResistanceAniline CompoundsAnimalsCells, CulturedHumansMicrotubulesModels, MolecularMutationProtein Structure, QuaternaryProtein Structure, TertiaryToxoplasmaTubulinAniline CompoundsTubulin

Identifiers

PMID17881728
PMCPMC2096588
OpenAlexW2131961997

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.