ArticleMolecular biology of the cell2007
Mutations in alpha-tubulin confer dinitroaniline resistance at a cost to microtubule function.
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.
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Who cites it
20 citing papers in PubMed, 50 citations in OpenAlex.
- Adaptations in Plasmodium tubulin determine distinct microtubule architectures, mechanics and drug susceptibility.Nature communications · 2026Article
- Assessing fitness costs in malaria parasites: a comprehensive review and implications for drug resistance management.Malaria journal · 2025Review
- Unveiling the Possible Oryzalin-Binding Site in the α-Tubulin ofACS omega · 2022Article
- Molecular Evolution of Tubulins in Diatoms.International journal of molecular sciences · 2022Article
- Microtubules in Microorganisms: How Tubulin Isotypes Contribute to Diverse Cytoskeletal Functions.Frontiers in cell and developmental biology · 2022Review
- Inhibiting parasite proliferation using a rationally designed anti-tubulin agent.EMBO molecular medicine · 2021Article
- Dinitroaniline Herbicide Resistance and Mechanisms in Weeds.Frontiers in plant science · 2021Review
- Chlamydomonas reinhardtii tubulin-gene disruptants for efficient isolation of strains bearing tubulin mutations.PloS one · 2020Article
- Alveolar proteins stabilize cortical microtubules in Toxoplasma gondii.Nature communications · 2019Article
- Drug Resistance inFrontiers in microbiology · 2018Review
- Novel α-Tubulin Mutations Conferring Resistance to Dinitroaniline Herbicides inFrontiers in plant science · 2018Article
- Article
- Targeting Toxoplasma tubules: tubulin, microtubules, and associated proteins in a human pathogen.Eukaryotic cell · 2015Review
- Article
- SPM1 stabilizes subpellicular microtubules in Toxoplasma gondii.Eukaryotic cell · 2012Article
- Article
- α-Tubulin mutations alter oryzalin affinity and microtubule assembly properties to confer dinitroaniline resistance.Eukaryotic cell · 2010Article
- Dinitroaniline activity in Toxoplasma gondii expressing wild-type or mutant alpha-tubulin.Antimicrobial agents and chemotherapy · 2010Article
- Secondary mutations correct fitness defects in Toxoplasma gondii with dinitroaniline resistance mutations.Genetics · 2008Article
- Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
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.
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