Cited by 30Antifungal resistance and susceptibilityFungal and yeast genetics researchDrug Transport and Resistance Mechanisms

Key physiological differences in Candida albicans CDR1 induction by steroid hormones and antifungal drugs

Larsen, Bryan, Anderson, Seth, Brockman, Andrea, Essmann, Michael, Schmidt, Martin·2006·Yeast

Abstract

The Candida albicans CDR1 gene, encoding an ABC transporter that functions as an efflux pump, is thought to be involved in pathogenic adaptation and uses mammalian hormones and other environmental cues to regulate its activity. Exposure of several clinical isolates of C. albicans to 1 × 10−8 M 17β‐oestradiol increased CDR1 expression and the isolates showed a positive correlation between oestrogen induction of CDR1 and growth in the presence of oestrogen. A reporter strain carrying the GFP gene under the control of the CDR1 promoter was used to analyse the effect of steroid hormones and antifungal drugs on CDR1 expression by flow cytometry. We found that among the many hormones tested, only oestradiol and progesterone induce CDR1 expression. CDR1 induction requires hormone concentrations greater than 10−8 M, a threshold reached in vivo only by progesterone. Using the GFP‐reporter strain, we show CDR1 induction by female but not male human serum and demonstrate that exposure of C. albicans to physiological concentrations of progesterone measurably increases resistance to fluconazole, miconazole and 5‐fluorouracil. Simultaneous exposure of C. albicans to hormones and antifungal drugs provided evidence that both agents induce CDR1 expression via different mechanisms with different saturation points. Copyright © 2006 John Wiley & Sons, Ltd.

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Crossref · 10.1002/yea.1394

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  • The expression of the drug exporting pump Cdr1p increases after exposure to a variety of stress factors and is considered a useful reporter for intracellular stress.

    “The expression of the drug exporting pump Cdr1p increases after exposure to a variety of stress factors and is considered a useful reporter for intracellular stress [8].”

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Authors
Larsen, B., Anderson, S., Brockman, A., Essmann, M., & Schmidt, M.
Affiliations
Des Moines University (US)
Corresponding author
Schmidt, Martin
Venue
Yeast
Publisher
Wiley
Published
2006-08
Volume
23
Issue
11
Pages
795-802
ISSN
  • 0749-503X (ISSN-L)
  • 1097-0061
OpenAlex
W2098243074
Cited by
30
References
24
Citations by year
2025: 1 · 2024: 2 · 2023: 1 · 2021: 3 · 2020: 2 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 3
FWCI
2.05
Type
journal article
Language
en
Open access
closed
Locations
  • Yeast (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
Candida albicans, CDR1, ABC transporters, efflux pumps, steroid hormones, estradiol, progesterone, antifungal resistance, fluconazole, miconazole, 5-fluorouracil, gene expression regulation, human serum, GFP reporter
MeSH terms
Antifungal Agents, Candida albicans, Estradiol, Female, Flow Cytometry, Fungal Proteins, Humans, Male, Progesterone, Drug Resistance, Fungal, Membrane Transport Proteins, Green Fluorescent Proteins

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