AUTHOR=Wasi Mohd , Khandelwal Nitesh Kumar , Moorhouse Alexander J. , Nair Remya , Vishwakarma Poonam , Bravo Ruiz Gustavo , Ross Zoe K. , Lorenz Alexander , Rudramurthy Shivaprakash M. , Chakrabarti Arunaloke , Lynn Andrew M. , Mondal Alok K. , Gow Neil A. R. , Prasad Rajendra 

TITLE=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

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.01445

DOI=10.3389/fmicb.2019.01445

ISSN=1664-302X

ABSTRACT=<p>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 <italic>Candida</italic> species. <italic>Candida auris</italic>, 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 <italic>C. auris</italic>. Our bioinformatics analyses identified 28 putative ABC proteins encoded in the genome of the <italic>C. auris</italic> 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 <italic>C. auris</italic> drug-resistant phenotype. Changes in transcript levels after short-term exposure of drugs and in drug-resistant <italic>C. auris</italic> isolates suggested their importance in the drug resistance phenotype of this pathogen. <italic>CAUR_02725</italic> orthologous to <italic>CDR1</italic>, a major multidrug exporter in other yeasts, showed consistently higher expression in multidrug-resistant strains of <italic>C. auris</italic>. Homologs of other ABC transporter genes, such as <italic>CDR4</italic>, <italic>CDR6</italic>, and <italic>SNQ2</italic>, also displayed raised expression in a sub-set of clinical isolates. Together, our analysis supports the involvement of these transporters in multidrug resistance in <italic>C. auris</italic>.</p>