Overexpression of Aldo-Keto-reductase in Azole-resistant clinical isolates of Candida glabrata determined by cDNA-AFLP
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BACKGROUND: Candida glabrata causes significant medical problems in immunocompromised patients. Many strains of this yeast are intrinsically resistant to azole antifungal agents, and treatment is problematic, leading to high morbidity and mortality rates in immunosuppressed individuals. The primary goal of this study was to investigate the genes involved in the drug resistance of clinical isolates of C. glabrata. METHODS: The clinical isolates of C. glabrata were collected in an epidemiological survey of candidal infection in immunocompromised patients and consisted of four fluconazole and itraconazole resistant isolates, two fluconazole and itraconazole sensitive isolates, and C. glabrata CBS 138 as reference strain. Antifungal susceptibility patterns of the organisms were determined beforehand by the Clinical and Laboratory Standards Institute (CLSI). The potential gene(s) implicated in antifungal resistance were investigated using complementary DNA- Amplified Fragment Length Polymorphism (cDNA-AFLP). Semi-quantitative RT-PCR was carried out to evaluate the expression of gene(s) in resistant isolates as compared to sensitive and reference strains. RESULTS AND CONCLUSIONS: The aldo-keto-reductase superfamily (AKR gene) was upregulated in the resistant clinical isolates as assessed by cDNA-AFLP. Semi-quantitative RT-PCR revealed AKR mRNA expression approximately twice that seen in the sensitive isolates. Overexpression of the AKR gene was associated with increased fluconazole and itraconazole resistance in C. glabrata. The data suggest that upregulation of the AKR gene might give a new insight into the mechanism of azole resistance.
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Candida glabrata clinical isolates are known to have the aldo-keto-reductase superfamily upregulated in the resistant isolates.
“Candida glabrata clinical isolates are known to have the aldo-keto-reductase superfamily upregulated in the resistant isolates.”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [109]
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- Authors
- Farahyar, S., Zaini, F., Kordbacheh, P., Rezaie, S., Safara, M., Raoofian, R., & Heidari, M.
- Affiliations
- Tehran University of Medical Sciences (IR)
- Mashhad University of Medical Sciences (IR)
- Corresponding author
- Zaini, Farideh
- Venue
- DARU Journal of Pharmaceutical Sciences
- Published
- 2013-01-02
- Volume
- 21
- Issue
- 1
- Pages
- 1-1
- ISSN
- 1560-8115 (ISSN-L)
- 2008-2231
- PMC
- PMC3556022
- OpenAlex
- W2140631543
- Cited by
- 125
- References
- 32
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 1 · 2021: 17 · 2020: 15 · 2019: 23 · 2018: 10 · 2017: 24 · 2016: 14 · 2015: 5 · 2014: 9 · 2013: 5
- FWCI
- 8.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- DARU Journal of Pharmaceutical Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Tehran University of Medical Sciences and Health Services
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- Candida glabrata, azole resistance, aldo-keto reductase, fluconazole resistance, itraconazole resistance, antifungal resistance, gene overexpression, immunocompromised patients, candidiasis, clinical isolates
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