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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

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 r...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647914/
https://www.ncbi.nlm.nih.gov/pubmed/31379756
http://dx.doi.org/10.3389/fmicb.2019.01445
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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
author_facet 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
author_sort Wasi, Mohd
collection PubMed
description 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.
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spelling pubmed-66479142019-08-02 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 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 Front Microbiol Microbiology 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. Frontiers Media S.A. 2019-07-16 /pmc/articles/PMC6647914/ /pubmed/31379756 http://dx.doi.org/10.3389/fmicb.2019.01445 Text en Copyright © 2019 Wasi, Khandelwal, Moorhouse, Nair, Vishwakarma, Bravo Ruiz, Ross, Lorenz, Rudramurthy, Chakrabarti, Lynn, Mondal, Gow and Prasad. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
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
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647914/
https://www.ncbi.nlm.nih.gov/pubmed/31379756
http://dx.doi.org/10.3389/fmicb.2019.01445
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