Evidence map›Paper›PMID 15388433›Full record

ArticleAntimicrobial agents and chemotherapy2004

Azole resistance in Candida glabrata: coordinate upregulation of multidrug transporters and evidence for a Pdr1-like transcription factor.

John-Paul Vermitsky, Thomas D Edlind

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.

0numbers the graph read from it
0cells of the map it votes in
155citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

155 citing papers in PubMed, 279 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. bioRxiv : the preprint server for biology · 2026
    Article
  5. Article
  6. The azole-resistance phenotype of aMicrobiology spectrum · 2026
    Article
  7. Yeast as a Model for Human Disease.International journal of molecular sciences · 2026
    Review
  8. Article
  9. Frontiers in microbiology · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Bixin fromACS omega · 2025
    Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article

95 more citing papers are in PubMed but not listed here.

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

2 authors at 1 institution in 1 country.

John-Paul VermitskyDepartment of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Ln., Philadelphia, PA 19129, USA. vermitsky@drexel.edu
Thomas D Edlind
Drexel University · US

Funding

Signaling Pathways in Yeast Azole ResponseR01AI047718 · NIAID · MCP HAHNEMANN UNIVERSITY · PI EDLIND, THOMAS D · 2001 to 2005
$1.2M
ANTIFUNGAL RESPONSE--MDR INDUCTIONR01AI046768 · NIAID · MCP HAHNEMANN UNIVERSITY · PI EDLIND, THOMAS D · 1999 to 2002
$536k
NIAID NIH HHS AI46768NIAID NIH HHS AI47718NIAID NIH HHS R01 AI047718
6 · The paper itself

Abstract

Candida glabrata has emerged as a common cause of fungal infection. This yeast has intrinsically low susceptibility to azole antifungals such as fluconazole, and mutation to frank azole resistance during treatment has been documented. Potential resistance mechanisms include changes in expression or sequence of ERG11 encoding the azole target. Alternatively, resistance could result from upregulated expression of multidrug transporter genes; in C. glabrata these include CDR1 and PDH1. By RNA hybridization, 10 of 12 azole-resistant clinical isolates showed 6- to 15-fold upregulation of CDR1 compared to susceptible strains. In 4 of these 10 isolates PDH1 was similarly upregulated, and in the remainder it was upregulated three- to fivefold, while ERG11 expression was minimally changed. Laboratory mutants were selected on fluconazole-containing medium with glycerol as carbon source (to eliminate mitochondrial mutants). Similar to the clinical isolates, six of seven laboratory mutants showed unchanged ERG11 expression but coordinate CDR1-PDH1 upregulation ranging from 2- to 20-fold. Effects of antifungal treatment on gene expression in susceptible C. glabrata strains were also studied: azole exposure induced CDR1-PDH1 expression 4- to 12-fold. These findings suggest that these transporter genes are regulated by a common mechanism. In support of this, a mutation associated with laboratory resistance was identified in the C. glabrata homolog of PDR1 which encodes a regulator of multidrug transporter genes in Saccharomyces cerevisiae. The mutation falls within a putative activation domain and was associated with PDR1 autoupregulation. Additional regulatory factors remain to be identified, as indicated by the lack of PDR1 mutation in a clinical isolate with coordinately upregulated CDR1-PDH1.

Indexed as

Amino Acid SequenceAntifungal AgentsAzolesCandida glabrataCarrier ProteinsCloning, MolecularDNA-Binding ProteinsDNA, FungalDrug Resistance, FungalFluconazoleMicrobial Sensitivity TestsMolecular Sequence DataRNA, FungalSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTrans-ActivatorsAntifungal AgentsAzolesCarrier ProteinsDNA-Binding ProteinsDNA, FungalFluconazolePDR1 protein, S cerevisiaeRNA, FungalSaccharomyces cerevisiae ProteinsTrans-ActivatorsTranscription Factors

Identifiers

PMID15388433
PMCPMC521908
OpenAlexW2166069926

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.