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

Frontiers in Microbiology

卷:10

Rajendra Prasad¹  Remya Nair¹  Arunaloke Chakrabarti²  Shivaprakash M. Rudramurthy²  Alexander J. Moorhouse³  Neil A. R. Gow⁴  Poonam Vishwakarma⁵  Andrew M. Lynn⁵  Nitesh Kumar Khandelwal⁶  Alok K. Mondal⁶  Mohd Wasi⁶  Alexander Lorenz⁷  Zoe K. Ross⁷  Gustavo Bravo Ruiz⁷ 

[1] Amity Institute of Biotechnology and Integrative Sciences and Health, Amity University Gurugram, Gurgaon, India;

[2] Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India;

[3] MRC Centre for Medical Mycology, University of Aberdeen, Aberdeen, United Kingdom;

[4] School of Biosciences, University of Exeter, Exeter, United Kingdom;

[5] School of Computational and Integrative Science, Jawaharlal Nehru University, New Delhi, India;

[6] School of Life Sciences, Jawaharlal Nehru University, New Delhi, India;

[7] The Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom;

关键词: Candida auris;    multidrug resistance;    ABC proteins;    drug efflux pumps;    fluconazole;   

DOI  :  10.3389/fmicb.2019.01445

来源: DOAJ

【 摘 要 】

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, 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 (TMDs). Quantitative real-time PCR confirmed the expression of all 20 TMD 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.

【 授权许可】

Unknown