ABC Transporter Genes Show Upregulated Expression in Drug-Resistant Clinical Isolates of Candida auris: A Genome-Wide Characterization of ATP-Binding Cassette (ABC) Transporter Genes
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ATP-binding cassette (ABC) superfamily members have a key role as nutrient importers and exporters in bacteria. However, their role as drug exporters in eukaryotes brought this superfamily member to even greater prominence. The capacity of ABC transporters to efflux a broad spectrum of xenobiotics represents one of the major mechanisms of clinical multidrug resistance in pathogenic fungi including Candida species. Candida auris, a newly emerged multidrug-resistant fungal pathogen of humans that has been responsible for multiple outbreaks of drug-resistant infections in hospitals around the globe. Our study has analyzed the entire complement of ABC superfamily transporters to assess whether these play a major role in drug resistance mechanisms of C. auris. Our bioinformatics analyses identified 28 putative ABC proteins encoded in the genome of the C. auris type-strain CBS 10913T; 20 of which contain transmembrane domains. Quantitative real-time PCR confirmed the expression of all 20 transmembrane domain transporters, underlining their potential in contributing to the C. auris drug resistant phenotype. Changes in transcript levels after short-term exposure of drugs and in drug-resistant C. auris isolates suggested their importance in the drug resistance phenotype of this pathogen. CAUR_02725 orthologous to CDR1, a major multidrug exporter in other yeasts, showed consistently higher expression in multidrug-resistant strains of C. auris. Homologs of other ABC transporter genes, such as CDR4, CDR6 and SNQ2, also displayed raised expression in a sub-set of clinical isolates. Together, our analysis supports the involvement of these transporters in multidrug resistance in C. auris.
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The Candida auris genome includes a substantial number of efflux pump-encoding genes of both ABC and major facilitator superfamily classes.
“The C. auris genome has recently been revealed to include a substantial number of efflux pump-encoding genes of both the ABC and major facilitator superfamily (MFS) classes”
From Mutations in <i>TAC1B</i> : a Novel Genetic Determinant of Clinical Fluconazole Resistance in Candida auris (2020) · cites this paper as [19]
Triazole-resistant Candida auris isolates exhibit efflux pump activity up to 14-fold higher than that of Candida glabrata.
“triazole-resistant isolates of C. auris have been observed to exhibit efflux pump activity greatly exceeding (up to 14-fold higher) that of C. glabrata (17–19).”
From Mutations in <i>TAC1B</i> : a Novel Genetic Determinant of Clinical Fluconazole Resistance in Candida auris (2020) · cites this paper as [19]
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- Authors
- Wasi, M., Khandelwal, N. K., Moorhouse, A. J., Nair, R., Vishwakarma, P., Bravo Ruiz, G., Ross, Z. K., Lorenz, A., Rudramurthy, S. M., Chakrabarti, A., Lynn, A. M., Mondal, A. K., Gow, N. A. R., & Prasad, R.
- Affiliations
- Jawaharlal Nehru University (IN)
- University of Aberdeen (GB)
- Amity University Gurugram (IN)
- Post Graduate Institute of Medical Education and Research (IN)
- Corresponding author
- Prasad, Rajendra
- ORCID
- Venue
- Frontiers in Microbiology
- Publisher
- Frontiers Media SA
- Published
- 2019-07-16
- Volume
- 10
- Pages
- 1445-1445
- ISSN
- 1664-302X (ISSN-L)
- PMC
- PMC6647914
- OpenAlex
- W2959316280
- Cited by
- 89
- References
- 73
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 12 · 2023: 14 · 2022: 16 · 2021: 14 · 2020: 13
- FWCI
- 8.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Microbiology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UA Campus Repository (The University of Arizona) (acceptedVersion, cc-by)
- Aberdeen University Research Archive (Aberdeen University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Bristol Research (University of Bristol) (submittedVersion)
- Greater South Information System
- Funders
- Indian Council of Medical Research
- Department of Biotechnology, Ministry of Science and Technology
- Department of Science and Technology, Ministry of Science and Technology (EMR/2016/001927, DST PURSE)
- Wellcome Trust (101873/Z/13/Z, 200208/A/15/Z, 097377/Z11/Z, 212524/Z/18/Z)
- Medical Research Council (MR/N006364/1)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Candida auris, ABC transporters, multidrug resistance, drug efflux, CDR1, gene expression, clinical isolates, antifungal resistance
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