Cited by 89Antifungal resistance and susceptibilityDrug Transport and Resistance MechanismsFungal and yeast genetics research

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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Wasi, Mohd, Khandelwal, Nitesh Kumar, Moorhouse, Alexander J., Nair, Remya, Vishwakarma, Poonam, Bravo Ruiz, Gustavo, Ross, Zoe K., Lorenz, Alexander +6 more·2019·Frontiers in Microbiology

Abstract

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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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
Venue
Frontiers in Microbiology
Published
2019-07-16
Volume
10
Pages
1445-1445
ISSN
1664-302X (ISSN-L)
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
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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