Molecular aspects of fluconazole resistance development in Candida albicans
Abstract
Serial Candida albicans isolates from recurrent episodes of oropharyngeal candidosis (OPC) in four AIDS patients which became fluconazole‐resistant during therapy were analysed by molecular methods. The CARE‐2 fingerprint patterns of the isolates demonstrated that in all four patients fluconazole resistance developed in a previously more susceptible strain. In two cases resistance correlated with enhanced expression of genes encoding multiple drug resistance proteins that mediate active drug efflux. Enhanced mRNA levels of the CDR1/CDR2 genes encoding ABC transporters were observed in fluconazole‐resistant isolates from one patient compared with the corresponding susceptible isolates. The fluconazole‐resistant isolates from another patient exhibited high mRNA levels of the MDR1 gene encoding a membrane transport protein of the major facilitator superfamily that was not detectably expressed in any of the fluconazole‐susceptible isolates. These results demonstrate that in AIDS patients with recurrent OPC the development of fluconazole resistance is usually caused by molecular changes in a previously susceptible C. albicans strain from the same patient.
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Overexpression of the efflux transporter genes CDR1, CDR2, and MDR1 is a common mechanism of drug resistance in C. albicans.
“Overexpression of the efflux transporter genes CDR1 , CDR2 , and MDR1 is a common mechanism of drug resistance in this organism (10, 17, 26).”
From Gain-of-Function Mutations in <i>UPC2</i> Are a Frequent Cause of <i>ERG11</i> Upregulation in Azole-Resistant Clinical Isolates of Candida albicans (2012) · cites this paper as [10]
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Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences
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“Overexpression of the efflux transporter genes CDR1, CDR2, and MDR1 is a common mechanism of drug resistance in this organism (10, 17, 26).”
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The ABCs of Candida albicans multidrug transporter Cdr1
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Competitive Fitness of Fluconazole-Resistant Clinical Candida albicans Strains
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- Authors
- Franz, R., Ruhnke, M., & Morschhäuser, J.
- Affiliations
- University of Würzburg (DE)
- Humboldt-Universität zu Berlin (DE)
- Corresponding author
- Morschhäuser, J.
- Venue
- Mycoses
- Publisher
- Wiley
- Published
- 1999-09
- Volume
- 42
- Issue
- 7-8
- Pages
- 453-458
- ISSN
- 0027-5557 (ISSN-L)
- 0933-7407
- 1439-0507
- OpenAlex
- W2094138644
- Cited by
- 129
- References
- 2
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 1 · 2021: 7 · 2020: 9 · 2019: 2 · 2018: 6 · 2017: 7 · 2016: 1 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 3
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Mycoses (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
- fluconazole resistance, Candida albicans, AIDS, multidrug resistance, CDR1, CDR2, MDR1, ABC transporters, major facilitator superfamily, drug efflux, recurrent fungal infection
- MeSH terms
- Antifungal Agents, Candida albicans, Candidiasis, Oral, Drug Resistance, Microbial, Humans, Fluconazole, AIDS-Related Opportunistic Infections
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