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Cited by 25Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Plant Pathogen Control

Expression Patterns of ABC Transporter Genes in Fluconazole-Resistant Candida glabrata

Gohar, Atefeh Abdollahi, Badali, Hamid, Shokohi, Tahereh, Nabili, Mojtaba, Amirrajab, Nasrin, Moazeni, Maryam·2017·Mycopathologia
DOI 10.1007/s11046-016-0074-8
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Abstract

Clinical management of fungal diseases is compromised by the emergence of antifungal drug resistance in fungi, which leads to elimination of available drug classes as treatment options. An understanding of antifungal resistance at molecular level is, therefore, essential for the development of strategies to combat the resistance. This study presents the assessment of molecular mechanisms associated with fluconazole resistance in clinical Candida glabrata isolates originated from Iran. Taking seven distinct fluconazole-resistant C. glabrata isolates, real-time PCRs were performed to evaluate the alternations in the regulation of the genes involved in drug efflux including CgCDR1, CgCDR2, CgSNQ2, and CgERG11. Gain-of-function (GOF) mutations in CgPDR1 alleles were determined by DNA sequencing. Cross-resistance to fluconazole, itraconazole, and voriconazole was observed in 2.5 % of the isolates. In the present study, six amino acid substitutions were identified in CgPdr1, among which W297R, T588A, and F575L were previously reported, whereas D243N, H576Y, and P915R are novel. CgCDR1 overexpression was observed in 57.1 % of resistant isolates. However, CgCDR2 was not co-expressed with CgCDR1. CgSNQ2 was upregulated in 71.4 % of the cases. CgERG11 overexpression does not seem to be associated with azole resistance, except for isolates that exhibited azole cross-resistance. The pattern of efflux pump gene upregulation was associated with GOF mutations observed in CgPDR1. These results showed that drug efflux mediated by adenosine-5-triphosphate (ATP)-binding cassette transporters, especially CgSNQ2 and CgCDR1, is the predominant mechanism of fluconazole resistance in Iranian isolates of C. glabrata. Since some novel GOF mutations were found here, this study also calls for research aimed at investigating other new GOF mutations to reveal the comprehensive understanding about efflux-mediated resistance to azole antifungal agents.

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Crossref · 10.1007/s11046-016-0074-8

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  • By increasing the copy number of chromosomes containing drug resistance genes, aneuploidy leads to resistance against multiple antifungals including azoles and echinocandins.

    “By increasing the copy number of chromosomes containing drug resistance genes, such as those encoding transcription factors, efflux pumps or involved in ergosterol biosynthesis, aneuploidy leads to resistance against multiple antifungals. including azoles and echinocandins [99,129,154].”

    From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [154]

  • By altering gene dosage or expression levels, aneuploidy allows fungi to quickly adjust to adverse conditions without permanent genetic mutations, promoting survival in fluctuating environments.

    “By altering gene dosage or expression levels, aneuploidy allows fungi to quickly adjust to adverse conditions without permanent genetic mutations, promoting survival in fluctuating environments [99,129,145,152,154].”

    From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [154]

  • ATP-binding cassette transporters of drug efflux are mediated primarily by CgSNQ2 and CgCDR1 and CgCDR2 genes.

    “According to the findings of Gohar et al. [86] and Farahyar et al. [88], the ATP-binding cassette transporters of drug efflux is mediated primarily by Candida glabrata sensitivity to 4 Nitroquinoline N-oxide (CgSNQ2) and Candida glabrata Candida drug resistance 1 and 2 (CgCDR1 and CgCDR2) genes.”

    From Candida glabrata: pathogenicity and resistance mechanisms for adaptation and survival (2021) · cites this paper as [86]

  • C. glabrata possesses numerous resistance mechanisms to fluconazole, including fluctuation of gene regulation, genetic mutations, and cross-resistance among azole derivatives.

    “Candida glabrata possesses numerous resistance mechanisms to fluconazole, including fluctuation of gene regulation, genetic mutations, and cross-resistance among azole derivatives [86].”

    From Candida glabrata: pathogenicity and resistance mechanisms for adaptation and survival (2021) · cites this paper as [86]

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Authors
Gohar, A. A., Badali, H., Shokohi, T., Nabili, M., Amirrajab, N., & Moazeni, M.
Affiliations
  • Mazandaran University of Medical Sciences (IR)
  • Ahvaz Jundishapur University of Medical Sciences (IR)
Corresponding author
Moazeni, Maryam
ORCID
Venue
Mycopathologia
Publisher
Springer Science and Business Media LLC
Published
2016-10-15
Volume
182
Issue
3-4
Pages
273-284
ISSN
  • 0301-486X (ISSN-L)
  • 1573-0832
DOI
10.1007/s11046-016-0074-8
OpenAlex
W2531300932
Cited by
25
References
37
Citations by year
2025: 4 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 3 · 2017: 3
FWCI
3.08
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (unspecified)
Locations
  • Mycopathologia (publishedVersion)
  • PubMed (publishedVersion)
Funders
Mazandaran University of Medical Sciences (684)
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, fluconazole resistance, antifungal resistance, ABC transporters, drug efflux pumps, itraconazole, voriconazole, gene expression
MeSH terms
Antifungal Agents, Candidiasis, Humans, Iran, Microbial Sensitivity Tests, Fluconazole, Sequence Analysis, DNA, Itraconazole, ATP-Binding Cassette Transporters, Amino Acid Substitution, Mutation, Missense, Gene Expression Profiling, Drug Resistance, Fungal, Candida glabrata, Real-Time Polymerase Chain Reaction, Voriconazole

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