Genomewide Elucidation of Drug Resistance Mechanisms for Systemically Used Antifungal Drugs Amphotericin B, Caspofungin, and Voriconazole in the Budding Yeast

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dc.authoridKodedova, Marie/0000-0003-3423-2363
dc.authoridDundar, Muhammed/0000-0001-6509-2012
dc.authoridKOÇ, AHMET/0000-0003-3484-2137
dc.authoridZimmermannova, Olga/0000-0003-2538-4488
dc.authoridŞahin Akdeniz, Esra/0000-0003-2795-9652
dc.authoridSychrova, Hana/0000-0001-5967-5019
dc.authoridBalcioglu, Orhan/0000-0001-7582-984X
dc.authorwosidKodedova, Marie/B-7559-2012
dc.authorwosidDundar, Muhammed/AAN-1831-2020
dc.authorwosidKOÇ, AHMET/ABI-3322-2020
dc.authorwosidZimmermannova, Olga/B-7925-2012
dc.authorwosidŞahin Akdeniz, Esra/AHB-9054-2022
dc.authorwosidSychrova, Hana/B-1350-2012
dc.authorwosidercan, ilkcan/JMP-4587-2023
dc.contributor.authorBalkan, Cigdem
dc.contributor.authorErcan, Ilkcan
dc.contributor.authorIsik, Esin
dc.contributor.authorAkdeniz, Esra Sahin
dc.contributor.authorBalcioglu, Orhan
dc.contributor.authorKodedova, Marie
dc.contributor.authorZimmermannova, Olga
dc.date.accessioned2024-08-04T20:46:44Z
dc.date.available2024-08-04T20:46:44Z
dc.date.issued2019
dc.departmentİnönü Üniversitesien_US
dc.description.abstractThere are only a few antifungal drugs used systemically in treatment, and invasive fungal infections that are resistant to these drugs are an emerging problem in health care. In this study, we performed a high-copy-number genomic DNA (gDNA) library screening to find and characterize genes that reduce susceptibility to amphotericin B, caspofungin, and voriconazole in Saccharomyces cerevisiae. We identified the PDR16 and PMP3 genes for amphotericin B, the RMD9 and SWH1 genes for caspofungin, and the MRS3 and TRI1 genes for voriconazole. The deletion mutants for PDR16 and PMP3 were drug susceptible, but the other mutants had no apparent susceptibility. Quantitative-PCR analyses suggested that the corresponding drugs upregulated expression of the PDR16, PMP3, SWH1, and MRS3 genes. To further characterize these genes, we also profiled the global expression patterns of the cells after treatment with the antifungals and determined the genes and paths that were up-or downregulated. We also cloned Candida albicans homologs of the PDR16, PMP3, MRS3, and TRI1 genes and expressed them in S. cerevisiae. Heterologous expression of Candida homologs also provided reduced drug susceptibility to the budding yeast cells. Our analyses suggest the involvement of new genes in antifungal drug resistance.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey [TUBITAK 212T186]; Academy of Sciences of the Czech Republic (ASCR)en_US
dc.description.sponsorshipThis study was financially supported by the Scientific and Technological Research Council of Turkey (TUBITAK 212T186 to A.K.) and the Academy of Sciences of the Czech Republic (ASCR).en_US
dc.identifier.doi10.1128/AAC.02268-18
dc.identifier.issn0066-4804
dc.identifier.issn1098-6596
dc.identifier.issue9en_US
dc.identifier.pmid31209012en_US
dc.identifier.scopus2-s2.0-85071238873en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1128/AAC.02268-18
dc.identifier.urihttps://hdl.handle.net/11616/98923
dc.identifier.volume63en_US
dc.identifier.wosWOS:000483118000004en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAmer Soc Microbiologyen_US
dc.relation.ispartofAntimicrobial Agents and Chemotherapyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectamphotericin Ben_US
dc.subjectantifungal agentsen_US
dc.subjectcaspofunginen_US
dc.subjectdrug resistanceen_US
dc.subjectgenomicsen_US
dc.subjectmultidrug resistanceen_US
dc.subjectvoriconazoleen_US
dc.titleGenomewide Elucidation of Drug Resistance Mechanisms for Systemically Used Antifungal Drugs Amphotericin B, Caspofungin, and Voriconazole in the Budding Yeasten_US
dc.typeArticleen_US

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