Evidence map›Paper›PMID 25182640›Full record

ArticleAntimicrobial agents and chemotherapy2014

Disruption of the transcriptional regulator Cas5 results in enhanced killing of Candida albicans by Fluconazole.

Erin M Vasicek, Elizabeth L Berkow, Vincent M Bruno, Aaron P Mitchell, Nathan P Wiederhold, Katherine S Barker, P David Rogers

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 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

23 citing papers in PubMed, 36 citations in OpenAlex.

  1. mBio · 2026
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  3. [Electroencephalographic microstates in vestibular schwannoma patients with tinnitus].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023
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  8. Article
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  10. Article
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  12. Article
  13. Article
  14. Transcriptional Circuits Regulating Developmental Processes inFrontiers in cellular and infection microbiology · 2020
    Review
  15. Review
  16. Antimicrobial agents and chemotherapy · 2019
    Article
  17. Review
  18. Review
  19. Article
  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

7 authors at 4 institutions in 1 country.

Erin M VasicekDepartment of Clinical Pharmacy, College of Pharmacy, Memphis, Tennessee, USA.
Elizabeth L BerkowDepartment of Clinical Pharmacy, College of Pharmacy, Memphis, Tennessee, USA.
Vincent M BrunoDepartment of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Aaron P MitchellDepartment of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
Nathan P WiederholdSchool of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.
Katherine S BarkerDepartment of Clinical Pharmacy, College of Pharmacy, Memphis, Tennessee, USA.
P David RogersDepartment of Clinical Pharmacy, College of Pharmacy, Memphis, Tennessee, USA Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, Tennessee, USA progers3@uthsc.edu.
Carnegie Mellon University · USLe Bonheur Children's Hospital · USThe University of Texas Health Science Center at San Antonio · USUniversity of Maryland, Baltimore · 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
Large-scale analysis of Candida albicans gene functionR01AI057804 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MITCHELL, AARON P · 2004 to 2008
$2.9M
NIAID NIH HHS R01 AI057804NIAID NIH HHS R01 AI058145NIAID NIH HHS R01AI058145
6 · The paper itself

Abstract

Azole antifungal agents such as fluconazole exhibit fungistatic activity against Candida albicans. Strategies to enhance azole antifungal activity would be therapeutically appealing. In an effort to identify transcriptional pathways that influence the killing activity of fluconazole, we sought to identify transcription factors (TFs) involved in this process. From a collection of C. albicans strains disrupted for genes encoding TFs (O. R. Homann, J. Dea, S. M. Noble, and A. D. Johnson, PLoS Genet. 5:e1000783, 2009, http://dx.doi.org/10.1371/journal.pgen.1000783), four strains exhibited marked reductions in minimum fungicidal concentration (MFCs) in both RPMI and yeast extract-peptone-dextrose (YPD) media. One of these genes, UPC2, was previously characterized with regard to its role in azole susceptibility. Of mutants representing the three remaining TF genes of interest, one (CAS5) was unable to recover from fluconazole exposure at concentrations as low as 2 μg/ml after 72 h in YPD medium. This mutant also showed reduced susceptibility and a clear zone of inhibition by Etest, was unable to grow on solid medium containing 10 μg/ml fluconazole, and exhibited increased susceptibility by time-kill analysis. CAS5 disruption in highly azole-resistant clinical isolates exhibiting multiple resistance mechanisms did not alter susceptibility. However, CAS5 disruption in strains with specific resistance mutations resulted in moderate reductions in MICs and MFCs. Genome-wide transcriptional analysis was performed in the presence of fluconazole and was consistent with the suggested role of CAS5 in cell wall organization while also suggesting a role in iron transport and homeostasis. These findings suggest that Cas5 regulates a transcriptional network that influences the response of C. albicans to fluconazole. Further delineation of this transcriptional network may identify targets for potential cotherapeutic strategies to enhance the activity of the azole class of antifungals.

Indexed as

Antifungal AgentsCandida albicansCandidiasisCarrier ProteinsCell WallCytochrome P-450 Enzyme SystemFluconazoleGene Expression ProfilingGene Expression RegulationGene Knockout TechniquesGene Regulatory NetworksMicrobial Sensitivity TestsMolecular Sequence DataTranscription FactorsAntifungal AgentsCarrier ProteinsCas5 protein, Candida albicansCytochrome P-450 Enzyme SystemFluconazoleTranscription Factors

Identifiers

PMID25182640
PMCPMC4249418
OpenAlexW2131476324

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.