Evidence map›Paper›PMID 30532246›Full record

ArticlePloS one2018

Fluconazole induces ROS in Cryptococcus neoformans and contributes to DNA damage in vitro.

Congyue Annie Peng, Andrea A E Gaertner, Sarah Ana Henriquez, Diana Fang, Rodney J Colon-Reyes, Julia L Brumaghim, Lukasz Kozubowski

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

30 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Article
  3. The APSES transcription factor Swi6B upregulatesApplied and environmental microbiology · 2025
    Article
  4. Review
  5. Exposure of Cryptococcus neoformans to low nitrogen levels enhances virulence.International microbiology : the official journal of the Spanish Society for Microbiology · 2024
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Fungistatic Effect of Phthalide Lactones onMolecules (Basel, Switzerland) · 2023
    Article
  11. Frontiers in physiology · 2023
    Article
  12. Modulation of the nanoscale motion rate ofFrontiers in microbiology · 2023
    Article
  13. Review
  14. Article
  15. Oxidative stress response pathways in fungi.Cellular and molecular life sciences : CMLS · 2022
    Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. In vitro anti-Cryptococcus activity of diphenyl diselenide alone and in combination with amphotericin B and fluconazole.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2021
    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 1 institution in 1 country.

Congyue Annie PengDepartment of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, United States of America.ORCID 0000-0002-9992-5737
Andrea A E GaertnerDepartment of Chemistry, Clemson University, Clemson, South Carolina, United States of America.
Sarah Ana HenriquezDepartment of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, United States of America.
Diana FangDepartment of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, United States of America.ORCID 0000-0001-7644-0377
Rodney J Colon-ReyesDepartment of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, United States of America.
Julia L BrumaghimDepartment of Chemistry, Clemson University, Clemson, South Carolina, United States of America.
Lukasz KozubowskiDepartment of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, United States of America.ORCID 0000-0002-9560-782X
Clemson University · US

Funding

The role of acetate fermentation in Entamoeba histolytica growth and infectionP20GM109094 · NIGMS · CLEMSON UNIVERSITY · PI TEMESVARI, LESLY A · 2016 to 2020
$10.4M
Mechanisms of Fluconazole-Induced Aneuploidy in Cryptococcus NeoformansR15AI119801 · NIAID · CLEMSON UNIVERSITY · PI KOZUBOWSKI, LUKASZ · 2015 to 2015
$437k
NIAID NIH HHS R15 AI119801NIGMS NIH HHS P20 GM109094
6 · The paper itself

Abstract

Pathogenic basidiomycetous yeast, Cryptococcus neoformans, causes fatal meningitis in immunocompromised individuals. Fluconazole (FLC) is a fungistatic drug commonly administered to treat cryptococcosis. Unfortunately, FLC-resistant strains characterized by various degree of chromosomal instability were isolated from clinical patients. Importantly, the underlying mechanisms that lead to chromosomal instability in FLC-treated C. neoformans remain elusive. Previous studies in fungal and mammalian cells link chromosomal instability to the reactive oxygen species (ROS). This study provides the evidence that exposure of C. neoformans to FLC induces accumulation of intracellular ROS, which correlates with plasma membrane damage. FLC caused transcription changes of oxidative stress related genes encoding superoxide dismutase (SOD1), catalase (CAT3), and thioredoxin reductase (TRR1). Strikingly, FLC contributed to an increase of the DNA damage in vitro, when complexed with iron or copper in the presence of hydrogen peroxide. Strains with isogenic deletion of copper response protein metallothionein were more susceptible to FLC. Addition of ascorbic acid (AA), an anti-oxidant at 10 mM, reduced the inhibitory effects of FLC. Consistent with potential effects of FLC on DNA integrity and chromosomal segregation, FLC treatment led to elevated transcription of RAD54 and repression of cohesin-encoding gene SCC1. We propose that FLC forms complexes with metals and contributes to elevated ROS, which may lead to chromosomal instability in C. neoformans.

Indexed as

Coordination ComplexesCryptococcus neoformansDNA DamageDrug Resistance, FungalFluconazoleGene Expression Regulation, FungalIn Vitro TechniquesMicrobial Sensitivity TestsOxidation-ReductionOxidative StressReactive Oxygen SpeciesUp-RegulationCoordination ComplexesFluconazoleReactive Oxygen Species

Identifiers

PMID30532246
PMCPMC6286144
OpenAlexW2903911795

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.