Evidence map›Paper›PMID 24936593›Full record

ArticleAntimicrobial agents and chemotherapy2014

SAGA/ADA complex subunit Ada2 is required for Cap1- but not Mrr1-mediated upregulation of the Candida albicans multidrug efflux pump MDR1.

Bernardo Ramírez-Zavala, Selene Mogavero, Eva Schöller, Christoph Sasse, P David Rogers, Joachim Morschhäuser

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

16 citing papers in PubMed, 26 citations in OpenAlex.

  1. Antifungal and Immunomodulatory Activities of Brazilian SavannahPharmaceuticals (Basel, Switzerland) · 2025
    Article
  2. Article
  3. Article
  4. Oxidative stress response pathways in fungi.Cellular and molecular life sciences : CMLS · 2022
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. A Potential Antifungal Effect of Chitosan AgainstFrontiers in microbiology · 2019
    Article
  10. Deletion ofAntimicrobial agents and chemotherapy · 2018
    Article
  11. Research of Mrr1, Cap1 and MDR1 inExperimental and therapeutic medicine · 2018
    Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. 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 at 2 institutions in 3 countries.

Bernardo Ramírez-ZavalaInstitut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Germany.
Selene MogaveroInstitut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Germany Department of Biology, University of Pisa, Pisa, Italy.
Eva SchöllerInstitut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Germany.
Christoph SasseInstitut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Germany.
P David RogersDepartment of Clinical Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Joachim MorschhäuserInstitut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Germany joachim.morschhaeuser@uni-wuerzburg.de.
University of Würzburg · DEUniversity of Tennessee Health Science Center · US

Funding

Novel Azole Resistance Mechanisms in Candida albicansR01AI058145 · NIAID · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI ROGERS, P. DAVID · 2005 to 2021
$5.8M
Novel Azole Resistance Mechanisms in Candida albicansR21AI058145 · NIAID · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI ROGERS, P DAVID · 2004 to 2004
$292k
NIAID NIH HHS AI058145NIAID NIH HHS R01 AI058145NIAID NIH HHS R21 AI058145
6 · The paper itself

Abstract

Overexpression of the multidrug efflux pump MDR1 is one mechanism by which the pathogenic yeast Candida albicans develops resistance to the antifungal drug fluconazole. The constitutive upregulation of MDR1 in fluconazole-resistant, clinical C. albicans isolates is caused by gain-of-function mutations in the zinc cluster transcription factor Mrr1. It has been suggested that Mrr1 activates MDR1 transcription by recruiting Ada2, a subunit of the SAGA/ADA coactivator complex. However, MDR1 expression is also regulated by the bZIP transcription factor Cap1, which mediates the oxidative stress response in C. albicans. Here, we show that a hyperactive Mrr1 containing a gain-of-function mutation promotes MDR1 overexpression independently of Ada2. In contrast, a C-terminally truncated, hyperactive Cap1 caused MDR1 overexpression in a wild-type strain but only weakly in mutants lacking ADA2. In the presence of benomyl or H2O2, compounds that induce MDR1 expression in an Mrr1- and Cap1-dependent fashion, MDR1 was upregulated with the same efficiency in wild-type and ada2Δ cells. These results indicate that Cap1, but not Mrr1, recruits Ada2 to the MDR1 promoter to induce the expression of this multidrug efflux pump and that Ada2 is not required for MDR1 overexpression in fluconazole-resistant C. albicans strains containing gain-of-function mutations in Mrr1.

Indexed as

ATP Binding Cassette Transporter, Subfamily B, Member 1Basic-Leucine Zipper Transcription FactorsCandida albicansCell Cycle ProteinsDrug Resistance, Multiple, FungalFluconazoleFungal ProteinsGene Expression Regulation, FungalHydrogen PeroxideMutationPromoter Regions, GeneticTranscriptional ActivationUp-RegulationATP Binding Cassette Transporter, Subfamily B, Member 1Basic-Leucine Zipper Transcription FactorsCAP1 protein, Candida albicansCell Cycle ProteinsFluconazoleFungal ProteinsHydrogen Peroxide

Identifiers

PMID24936593
PMCPMC4135829
OpenAlexW2123351425

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.