Evidence map›Paper›PMID 12183235›Full record

ArticleAntimicrobial agents and chemotherapy2002

The Candida dubliniensis CdCDR1 gene is not essential for fluconazole resistance.

Gary Moran, Derek Sullivan, Joachim Morschhäuser, David Coleman

Abstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

18 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Depletion of theMicrobiology (Reading, England) · 2026
    Article
  3. Fluconazole resistance andMicrobiology (Reading, England) · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Xenobiotic efflux in bacteria and fungi: a genomics update.Advances in enzymology and related areas of molecular biology · 2011
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. ThemSphere
    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.

Gary MoranMicrobiology Research Unit, Department of Oral Surgery, Oral Medicine and Pathology, School of Dental Science, Trinity College, University of Dublin, Republic of Ireland.
Derek Sullivan
Joachim Morschhäuser
David Coleman

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The present study investigated the role of the Candida dubliniensis CdCDR1 and CdCDR2 genes in the development of fluconazole resistance. The C. dubliniensis CdCDR1 gene was 92% identical at the nucleotide sequence level to the corresponding C. albicans gene. However, 58% (14 of 24) of C. dubliniensis genotype 1 isolates tested harbored a nonsense mutation in the CdCDR1 open reading frame that converted codon 756 (TAT) to a TAG translational stop codon. Analysis of five of these C. dubliniensis isolates by Western immunoblotting showed that they expressed a truncated 85-kDa CdCdr1p compared to the full-length 170-kDa CdCdr1p. Expression of CdCDR1 alleles from six C. dubliniensis isolates in a pdr5 Saccharomyces cerevisiae strain revealed that CdCDR1 alleles from three isolates that encoded truncated proteins were unable to confer resistance to drugs and antifungals. However, reassignment of the TAG sequence at codon 756 to TAT (encoding tyrosine) in an allele from strain CD36 conferred the ability to mediate resistance to multiple drugs. Fluconazole-resistant isolates of C. dubliniensis harboring functional alleles of CdCDR1 were found to exhibit two- to ninefold-higher levels of CdCDR1 mRNA than did matched fluconazole-susceptible isolates. By comparison, levels of CdMDR1 expression ranged from approximately 50- to 100-fold greater in resistant isolates. Fluconazole resistance was also identified in isolates harboring nonfunctional CdCDR1 alleles, but resistance in these isolates was only associated with increased CdMDR1 expression. Targeted disruption of two functional alleles of CdCDR1 in a fluconazole-resistant derivative of C. dubliniensis that overexpressed both CdCDR1 and CdMDR1 revealed that although CdCDR1 was important for mediating reduced susceptibility to itraconazole and ketoconazole, there was no affect on fluconazole susceptibility in the double mutant. Evidence presented in this study reveals that CdCDR1 is not essential for the development of fluconazole resistance in C. dubliniensis.

Indexed as

AllelesAntifungal AgentsATP-Binding Cassette TransportersAzolesBlotting, SouthernBlotting, WesternCandidaDNA, FungalDNA PrimersDrug Resistance, FungalFluconazoleFungal ProteinsGene TargetingMembrane Transport ProteinsMutagenesis, Site-DirectedReverse Transcriptase Polymerase Chain ReactionAntifungal AgentsATP-Binding Cassette TransportersAzolesCDR1 protein, Candida albicansDNA, FungalDNA PrimersFluconazoleFungal ProteinsMembrane Transport ProteinsRNA, Messenger

Identifiers

PMID12183235
PMCPMC127416

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.