Evidence map›Paper›PMID 10629186›Full record

ArticleJournal of bacteriology2000

Activation of the multiple drug resistance gene MDR1 in fluconazole-resistant, clinical Candida albicans strains is caused by mutations in a trans-regulatory factor.

S Wirsching, S Michel, G Köhler, J Morschhäuser

Open access · greenAbstract read
In one paragraph

Article in Journal of bacteriology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

42 citing papers in PubMed, 87 citations in OpenAlex.

  1. EditingBiomolecules · 2026
    Review
  2. Comparative evaluation of biologically and chemically synthesized zinc oxide nanoparticles for preventing Candida auris biofilm.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025
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  7. Repurposing pantoprazole and haloperidol as efflux pump inhibitors in azole resistant clinicalSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022
    Article
  8. Application of Green AlgalMolecules (Basel, Switzerland) · 2021
    Article
  9. Article
  10. Article
  11. Review
  12. CRISPR-Based Genetic Manipulation ofFrontiers in genome editing · 2020
    Review
  13. Candida parapsilosis: from Genes to the Bedside.Clinical microbiology reviews · 2019
    Review
  14. Review
  15. Frontiers in microbiology · 2018
    Review
  16. Article
  17. Review
  18. Article
  19. Review
  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

4 authors at 1 institution in 1 country.

S WirschingZentrum für Infektionsforschung, Universität Würzburg, Röntgenring 11, D-97070 Würzburg, Germany.
S Michel
G Köhler
J Morschhäuser
University of Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Resistance of Candida albicans against the widely used antifungal agent fluconazole is often due to active drug efflux from the cells. In many fluconazole-resistant C. albicans isolates the reduced intracellular drug accumulation correlates with constitutive strong expression of the MDR1 gene, encoding a membrane transport protein of the major facilitator superfamily that is not detectably expressed in vitro in fluconazole-susceptible isolates. To elucidate the molecular changes responsible for MDR1 activation, two pairs of matched fluconazole-susceptible and resistant isolates in which drug resistance coincided with stable MDR1 activation were analyzed. Sequence analysis of the MDR1 regulatory region did not reveal any promoter mutations in the resistant isolates that might account for the altered expression of the gene. To test for a possible involvement of trans-regulatory factors, a GFP reporter gene was placed under the control of the MDR1 promoter from the fluconazole-susceptible C. albicans strain CAI4, which does not express the MDR1 gene in vitro. This MDR1P-GFP fusion was integrated into the genome of the clinical C. albicans isolates with the help of the dominant selection marker MPA(R) developed for the transformation of C. albicans wild-type strains. Integration was targeted to an ectopic locus such that no recombination between the heterologous and resident MDR1 promoters occurred. The transformants of the two resistant isolates exhibited a fluorescent phenotype, whereas transformants of the corresponding susceptible isolates did not express the GFP gene. These results demonstrate that the MDR1 promoter was activated by a trans-regulatory factor that was mutated in fluconazole-resistant isolates, resulting in deregulated, constitutive MDR1 expression.

Indexed as

Gene Expression Regulation, FungalGenes, RegulatorMutationATP Binding Cassette Transporter, Subfamily B, Member 1Candida albicansDrug Resistance, MultipleFluconazoleGreen Fluorescent ProteinsLuminescent ProteinsPromoter Regions, GeneticRecombinant Fusion ProteinsRNA, MessengerSequence Analysis, DNAATP Binding Cassette Transporter, Subfamily B, Member 1FluconazoleGreen Fluorescent ProteinsLuminescent ProteinsRecombinant Fusion ProteinsRNA, Messenger

Identifiers

PMID10629186
PMCPMC94289
OpenAlexW2131106578

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.