Evidence map›Paper›PMID 30911079›Full record

ArticleScientific reports2019

Gene Duplication Associated with Increased Fluconazole Tolerance in Candida auris cells of Advanced Generational Age.

Somanon Bhattacharya, Thomas Holowka, Erika P Orner, Bettina C Fries

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
8.0field-weighted citation impact, top 2% 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

64 citing papers in PubMed, 96 citations in OpenAlex.

  1. Review
  2. Article
  3. Adaptive susceptibility shifts in Candidozyma auris following biocidal exposure: Exploratory effects on antifungal and biocidal susceptibility.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
    Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Microbiology spectrum · 2025
    Article
  10. Potent anti-biofilm properties of plumbagin against fluconazole-resistantJournal of traditional and complementary medicine · 2025
    Article
  11. Article
  12. Innate immune response to Candida auris.Current opinion in microbiology · 2024
    Review
  13. Comprehensive Overview ofJournal of microbiology and biotechnology · 2024
    Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Virulence Traits and Azole Resistance in KoreanJournal of fungi (Basel, Switzerland) · 2023
    Article
  19. Article
  20. Cell Aggregation Capability of Clinical Isolates fromTropical medicine and infectious disease · 2023
    Article

4 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

4 authors at 3 institutions in 1 country.

Somanon BhattacharyaDivision of Infectious Diseases, Department of Medicine, Stony Brook University, Stony Brook, New York, USA.
Thomas HolowkaDivision of Infectious Diseases, Department of Medicine, Stony Brook University, Stony Brook, New York, USA.
Erika P OrnerDivision of Infectious Diseases, Department of Medicine, Stony Brook University, Stony Brook, New York, USA.ORCID http://orcid.org/0000-0002-6253-7298
Bettina C FriesDivision of Infectious Diseases, Department of Medicine, Stony Brook University, Stony Brook, New York, USA. Bettina.Fries@stonybrookmedicine.edu.ORCID http://orcid.org/0000-0002-6847-5518
Stony Brook University · USStony Brook School · USYale University · US

Funding

MOLECULAR AND CELL BIOLOGY OF INFECTIOUS DISEASEST32AI007539 · NIAID · STATE UNIVERSITY NEW YORK STONY BROOK · PI KONOPKA, JAMES B · 1998 to 2023
$3.6M
Investigation on Replicative aging in Cryptococcus neoformans populationsR01AI127704 · NIAID · STATE UNIVERSITY NEW YORK STONY BROOK · PI FRIES, BETTINA · 2017 to 2021
$3.2M
Optimization of therapeutic mAbs to carbapenem resistant Klebsiella clone ST258I01BX003741 · VA · NORTHPORT VA MEDICAL CENTER · PI FRIES, BETTINA · 2019 to 2025
–
BLRD VA I01 BX003741NIAID NIH HHS R01 AI127704NIAID NIH HHS T32 AI007539
6 · The paper itself

Abstract

Candida auris is an emerging multi-drug resistant yeast that causes systemic infections. Here we show that C. auris undergoes replicative aging (RA) that results from asymmetric cell division and causes phenotypic differences between mother and daughter cells similar to other pathogenic yeasts. Importantly, older C. auris cells (10 generations) exhibited higher tolerance to fluconazole (FLC), micafungin, 5- flucytosine and amphotericin B compared to younger (0-3 generation) cells. Increased FLC tolerance was associated with increased Rhodamine 6G (R6G) efflux and therapeutic failure of FLC in a Galleria infection model. The higher efflux in the older cells correlated with overexpression of the efflux pump encoding gene CDR1 (4-fold). In addition, 8-fold upregulation of the azole target encoding gene ERG11 was noted in the older cells. Analysis of genomic DNA from older cells by qPCR indicates that transient gene duplication of CDR1 and ERG11 causes the observed age-dependent enhanced FLC tolerance in C. auris strains. Furthermore, older cells exhibited a thickened cell wall, decreased neutrophil killing (24% vs 50%), increased epithelial cell adhesion (31.6% vs 17.8%) and upregulation of adhesin protein Als5p. Thus, this study demonstrates that transient gene duplication can occur during RA, causing increased FLC tolerance in old C. auris cells.

Indexed as

Drug Resistance, FungalGene DuplicationAntifungal AgentsCandidaCellular SenescenceFluconazoleMicrobial Sensitivity TestsPhenotypeAntifungal AgentsFluconazole

Identifiers

PMID30911079
PMCPMC6434143
OpenAlexW2923761354

What OpenQuestion 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 OpenQuestion graph.