Cited by 40Fungal and yeast genetics researchAntifungal resistance and susceptibilityFungal Plant Pathogen Control

Metabolic control of antifungal drug resistance

Robbins, Nicole, Collins, Cathy, Morhayim, Jess, Cowen, Leah E.·2010·Fungal Genetics and Biology

Abstract

Fungi have evolved an elegant repertoire of mechanisms to survive the cellular stress exerted by antifungal drugs such as azoles, which inhibit ergosterol biosynthesis inducing cell membrane stress. The evolution and maintenance of diverse resistance phenotypes is contingent upon cellular circuitry regulated by the molecular chaperone Hsp90 and its client protein calcineurin. Here, we establish a novel role for nutrients and nutrient signaling in azole resistance. The vulnerability of Saccharomyces cerevisiae azole resistance phenotypes to perturbation was contingent upon specific auxotrophies. Using strains that acquired azole resistance by Erg3 loss of function as a model for resistance that depends on cellular stress responses, we delineated genetic and environmental factors that mitigate the translation of genotype into resistance phenotype. Compromising a global regulator that couples growth and metabolism to environmental cues, Tor kinase, provides a powerful strategy to abrogate drug resistance of S. cerevisiae and Candida albicans with broad therapeutic potential.

Integrity signals

Registry

Crossref · 10.1016/j.fgb.2009.07.004

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Loss-of-function of Erg3 confers a mode of resistance dependent upon Hsp90.

    “acquired by loss-of-function of Erg3, a mode of resistance dependent upon Hsp9086.”

    From Molecular mechanisms governing antifungal drug resistance (2023) · cites this paper as [86]

  • Rapamycin blocks azole resistance acquired by loss-of-function of Erg3, a mode of resistance dependent upon Hsp90.

    “In line with this, rapamycin blocks azole resistance acquired by loss-of-function of Erg3, a mode of resistance dependent upon Hsp9086.”

    From Molecular mechanisms governing antifungal drug resistance (2023) · cites this paper as [86]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Robbins, N., Collins, C., Morhayim, J., & Cowen, L. E.
Affiliations
University of Toronto (CA)
Corresponding author
Cowen, Leah E.
Venue
Fungal Genetics and Biology
Publisher
Elsevier BV
Published
2010-02
Volume
47
Issue
2
Pages
81-93
ISSN
1087-1845 (ISSN-L)
OpenAlex
W2018134501
Cited by
40
References
51
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 5
FWCI
1.74
Type
journal article
Language
en
Open access
closed
Locations
  • Fungal Genetics and Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research (MOP-86452)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Keywords
antifungal resistance, azole resistance, ergosterol biosynthesis, nutrient signaling, HSP90, calcineurin, TOR kinase, ERG3, auxotrophy, cellular stress response, Saccharomyces cerevisiae, Candida albicans
MeSH terms
Amino Acids, Antifungal Agents, Azoles, Culture Media, Microbial Sensitivity Tests, Mutation, Oxidoreductases, Phenotype, Saccharomyces cerevisiae, Signal Transduction, Gene Expression, Genome, Fungal, HSP90 Heat-Shock Proteins, Calcineurin, Sirolimus, Reverse Transcriptase Polymerase Chain Reaction, Drug Resistance, Fungal, Saccharomyces cerevisiae Proteins, Basic-Leucine Zipper Transcription Factors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review