{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:15:30Z","timestamp":1778220930901,"version":"3.51.4"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    <jats:italic>Candida (Candidozyma) auris<\/jats:italic>\n                    has recently been designated a critical priority pathogen by the World Health Organization (WHO) in its Fungal Priority Pathogens List (FPPL). With resistance now widespread against frontline antifungals and limited availability of alternative therapeutics, combination regimens incorporating the nucleoside analog flucytosine (5-fluorocytosine; 5-FC) have gained renewed attention. While transporter-mediated resistance is well established for azole antifungals, knowledge on the molecular basis underlying reduced susceptibility to 5-FC in\n                    <jats:italic>C. auris<\/jats:italic>\n                    remains limited. Here, we aimed to functionally characterize two\n                    <jats:italic>C. auris<\/jats:italic>\n                    DHA1 transporters and to evaluate whether their inhibition may modulate 5-FC efficacy. Building on earlier reports showing elevated expression of two major facilitator superfamily (MFS) transporters belonging to the Drug\/H\n                    <jats:sup>+<\/jats:sup>\n                    antiporter-1 (DHA1) family upon 5-FC exposure, we now provide functional evidence supporting their contribution to 5-FC resistance. Heterologous expression of these transporters, B9J08_002663 (CauQdr2) and B9J08_004113 (CauMdr1.2) in a\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    system resulted in a marked increase in 5-FC resistance, with a\u202f&amp;gt;\u202f2-fold shift in IC\u2085\u2080 values compared to the host strain. Moreover, analysis of ligand-bound structural models revealed a conserved interaction niche, consistent with structural and functional data from major facilitator superfamily (MFS) proteins, particularly DHA1 transporters. Furthermore, we also identified clorgyline as a selective inhibitor of CauMdr1.2, capable of modulating 5-FC susceptibility. Collectively, our findings uncover a DHA1 transporter-mediated mechanism of 5-FC resistance in\n                    <jats:italic>C. auris<\/jats:italic>\n                    , expanding the functional repertoire of such proteins and providing potential new targets for antifungal intervention. The findings further provide a rationale for designing 5-FC\u2013based combination strategies incorporating transporter inhibitors to enhance drug efficacy and counteract efflux-mediated resistance.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1806653","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:51:45Z","timestamp":1778219505000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional characterization of Candida auris DHA1 transporters conferring flucytosine resistance"],"prefix":"10.3389","volume":"17","author":[{"given":"Sarita","family":"Malik","sequence":"first","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University Haryana","place":["Gurugram, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amandeep","family":"Saini","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University Haryana","place":["Gurugram, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosy","family":"Khatoon","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University Haryana","place":["Gurugram, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atanu","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University Haryana","place":["Gurugram, India"]},{"name":"Amity Institute of Integrative Sciences and Health, Amity University Haryana","place":["Gurugram, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2884","DOI":"10.1016\/J.CSBJ.2023.04.025","article-title":"Structural characterization of the Aspergillus niger citrate transporter CexA uncovers the role of key residues S75, R192 and Q196","volume":"21","author":"Alves","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"7715","DOI":"10.1128\/AAC.02204-15","article-title":"Acquired multidrug antifungal resistance in Candida lusitaniae during therapy","volume":"59","author":"Asner","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"68","DOI":"10.3390\/jof7020068","article-title":"Directed mutational strategies reveal drug binding and transport by the MDR transporters of Candida albicans","volume":"7","author":"Banerjee","year":"2021","journal-title":"J. Fungi"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1093\/JAC\/DKG217","article-title":"Identification of genes differentially expressed in association with reduced azole susceptibility in Saccharomyces cerevisiae","volume":"51","author":"Barker","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e01393-19","DOI":"10.1128\/AAC.01393-19","article-title":"In vitro antifungal combination of flucytosine with amphotericin B, voriconazole, or micafungin against Candida auris shows no antagonism","volume":"63","author":"Bidaud","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1101\/2025.01.08.631967","article-title":"Protenix - advancing structure prediction through a comprehensive AlphaFold3 reproduction","author":"Chen","year":"2025","journal-title":"bioRxiv"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1128\/CMR.00051-08","article-title":"Efflux-mediated antifungal drug resistance","volume":"22","author":"Cannon","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.chembiol.2026.01.009","article-title":"Exporter Mdr1 as an importer is an achilles\u2019 heel for combating drug-resistant Candida","volume":"33","author":"Chen","year":"2026","journal-title":"Cell Chem. Biol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"170","DOI":"10.3389\/FMICB.2013.00170","article-title":"The dual role of Candida glabrata drug:H+ antiporter CgAqr1 (ORF CAGL0J09944g) in antifungal drug and acetic acid resistance","volume":"4","author":"Costa","year":"","journal-title":"Front. Microbiol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"3159","DOI":"10.1128\/AAC.00811-12","article-title":"Candida glabrata drug:H+ antiporter CgQdr2 confers imidazole drug resistance, being activated by transcription factor CgPdr1","volume":"57","author":"Costa","year":"","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"927","DOI":"10.3390\/microorganisms12050927","article-title":"Candida auris outbreaks: current status and future perspectives","volume":"12","author":"De Gaetano","year":"2024","journal-title":"Microorganisms"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"909","DOI":"10.3390\/JOF7110909","article-title":"Molecular mechanisms of 5-fluorocytosine resistance in yeasts and filamentous fungi","volume":"7","author":"Delma","year":"2021","journal-title":"J. Fungi"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e00807-19","DOI":"10.1128\/AAC.00807-19","article-title":"The siderophore transporter Sit1 determines susceptibility to the antifungal VL-2397","volume":"63","author":"Dietl","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1101\/2024.10.10.615955","article-title":"Chai-1: decoding the molecular interactions of life","author":"Discovery","year":"2024","journal-title":"bioRxiv"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1128\/EC.00008-13","article-title":"Roles of different peptide transporters in nutrient acquisition in Candida albicans","volume":"12","author":"Dunkel","year":"2013","journal-title":"Eukaryot. Cell"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1146\/ANNUREV-MED-061523-021233","article-title":"Candida auris: epidemiology and antifungal strategy","volume":"76","author":"Eix","year":"2025","journal-title":"Annu. Rev. Med."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/genes11111324","article-title":"Carrier-mediated drug uptake in fungal pathogens","volume":"11","author":"Galocha","year":"2020","journal-title":"Genes"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1128\/JB.182.6.1492-1498.2000","article-title":"The TetA(K) tetracycline\/H(+) antiporter from Staphylococcus aureus: mutagenesis and functional analysis of motif C","volume":"182","author":"Ginn","year":"2000","journal-title":"J. Bacteriol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"myac072P198","DOI":"10.1093\/MMY\/MYAC072.P198","article-title":"P198 persistent fungemia with Candida auris in a patient with enterocutaneous fistula","volume":"60","author":"Gohel","year":"2022","journal-title":"Med. Mycol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1038\/cr.2015.94","article-title":"Substrate-bound structure of the E. coli multidrug resistance transporter MdfA","volume":"25","author":"Heng","year":"2015","journal-title":"Cell Res."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"5246","DOI":"10.1128\/IAI.70.9.5246-5255.2002","article-title":"The siderophore iron transporter of Candida albicans (Sit1p\/Arn1p) mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion","volume":"70","author":"Heymann","year":"2002","journal-title":"Infect. Immun."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.4155\/fmc-2016-0050","article-title":"Targeting efflux pumps to overcome antifungal drug resistance","volume":"8","author":"Holmes","year":"2016","journal-title":"Future Med. Chem."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1128\/AAC.05706-11","article-title":"The monoamine oxidase a inhibitor clorgyline is a broad-spectrum inhibitor of fungal ABC and MFS transporter efflux pump activities which reverses the azole resistance of Candida albicans and Candida glabrata clinical isolates","volume":"56","author":"Holmes","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"W739","DOI":"10.1093\/NAR\/GKAC382","article-title":"SynergyFinder 3.0: an interactive analysis and consensus interpretation of multi-drug synergies across multiple samples","volume":"50","author":"Ianevski","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e0005322","DOI":"10.1128\/aac.00053-22","article-title":"Candida auris pan-drug-resistant to four classes of antifungal agents","volume":"66","author":"Jacobs","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e314","DOI":"10.1016\/S2666-5247(20)30194-4","article-title":"Micafungin and amphotericin B synergy against Candida auris","volume":"1","author":"Jaggavarapu","year":"2020","journal-title":"Lancet Microbe"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e0164522","DOI":"10.1128\/AAC.01645-22","article-title":"Heightened efficacy of anidulafungin when used in combination with manogepix or 5-flucytosine against Candida auris in vitro","volume":"67","author":"John","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e02512","DOI":"10.1128\/mBio.02512-19","article-title":"Comparative genomics for the elucidation of multidrug resistance in Candida lusitaniae","volume":"10","author":"Kannan","year":"2019","journal-title":"MBio"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"RP105333","DOI":"10.7554\/eLife.105333.1","article-title":"SATAY-based chemogenomic screening uncovers antifungal resistance mechanisms and key determinants of ATI-2307 and chitosan sensitivity","volume":"14","author":"Karadzas","year":"2025","journal-title":"eLife"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: improvements in performance and usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"4223","DOI":"10.1007\/s00253-022-11998-9","article-title":"Genome-wide analysis of PTR transporters in Candida species and their functional characterization in Candida auris","volume":"106","author":"Khatoon","year":"","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"7085","DOI":"10.1007\/s00253-022-12189-2","article-title":"Genomic landscape of the DHA1 family in Candida auris and mapping substrate repertoire of CauMdr1","volume":"106","author":"Khatoon","year":"","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"lxaf170","DOI":"10.1093\/jambio\/lxaf170","article-title":"The proton-dependent oligopeptide transporter Ptr_C serves as an efficient system for antifungal delivery into Candida auris","volume":"136","author":"Khatoon","year":"2025","journal-title":"J. Appl. Microbiol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1016\/j.cmi.2024.03.006","article-title":"New treatment options for critically important WHO fungal priority pathogens","volume":"31","author":"Kriegl","year":"2025","journal-title":"Clin. Microbiol. Infect."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1128\/EC.00091-07","article-title":"Characterization of three classes of membrane proteins involved in fungal azole resistance by functional hyperexpression in Saccharomyces cerevisiae","volume":"6","author":"Lamping","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"W293","DOI":"10.1093\/nar\/gkab301","article-title":"Interactive tree of life (iTOL) v5: an online tool for phylogenetic tree display and annotation","volume":"49","author":"Letunic","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"103243","DOI":"10.1016\/J.FGB.2019.103243","article-title":"Candida auris and multidrug resistance: defining the new normal","volume":"131","author":"Lockhart","year":"2019","journal-title":"Fungal Genet. Biol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1093\/cid\/ciw691","article-title":"Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses","volume":"64","author":"Lockhart","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.15585\/MMWR.MM7029A2","article-title":"Notes from the field: transmission of pan-resistant and echinocandin-resistant Candida auris in health care facilities \u2014 Texas and the District of Columbia, January\u2013April 2021","volume":"70","author":"Lyman","year":"2025","journal-title":"MMWR Morb. Mortal Wkly. Rep."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e62592","DOI":"10.3791\/62592","article-title":"Small-scale plasma membrane preparation for the analysis of Candida albicans Cdr1-mGFPHis","author":"Madani","year":"2021","journal-title":"JoVE"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"e482","DOI":"10.1016\/S2666-5247(23)00114-3","article-title":"Candida auris: an emerging antimicrobial-resistant organism with the highest level of concern","volume":"4","author":"Mishra","year":"2023","journal-title":"Lancet Microbe"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"e0180990","DOI":"10.1371\/journal.pone.0180990","article-title":"Unexpected effects of azole transporter inhibitors on antifungal susceptibility in Candida glabrata and other pathogenic Candida species","volume":"12","author":"Nagayoshi","year":"2017","journal-title":"PLoS One"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"e193","DOI":"10.1016\/S2666-5247(20)30090-2","article-title":"Pan-resistant Candida auris: New York subcluster susceptible to antifungal combinations","volume":"1","author":"O\u2019Brien","year":"2020","journal-title":"Lancet Microbe"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"229572","DOI":"10.3389\/FMICB.2016.02045","article-title":"Membrane proteomics analysis of the Candida glabrata response to 5-flucytosine: unveiling the role and regulation of the drug efflux transporters CgFlr1 and CgFlr2","volume":"7","author":"Pais","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1128\/EC.00315-06","article-title":"Structure and function analysis of CaMdr1p, a major facilitator superfamily antifungal efflux transporter protein of Candida albicans: identification of amino acid residues critical for drug\/H+ transport","volume":"6","author":"Pasrija","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.1101\/2025.06.14.659707","article-title":"Boltz-2: towards accurate and efficient binding affinity prediction","author":"Passaro","year":"2025","journal-title":"bioRxiv"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"e0123625","DOI":"10.1128\/aac.01236-25","article-title":"The siderophore transporter Sit1 is involved in the uptake of caspofungin by Candida albicans","volume":"70","author":"Pedras","year":"2026","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/pro.3943","article-title":"UCSF ChimeraX: structure visualization for researchers, educators, and developers","volume":"30","author":"Pettersen","year":"2021","journal-title":"Protein Sci."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"e0097724","DOI":"10.1128\/MSPHERE.00977-24","article-title":"Rapid in vitro evolution of flucytosine resistance in Candida auris","volume":"10","author":"Phan-Canh","year":"2025","journal-title":"mSphere"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1128\/MMBR.64.4.672-693.2000","article-title":"Molecular properties of bacterial multidrug transporters","volume":"64","author":"Putman","year":"2000","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"100354","DOI":"10.1016\/J.CRMICR.2025.100354","article-title":"The multidrug-resistant Candida auris, Candida haemulonii complex and phylogenetic related species: insights into antifungal resistance mechanisms","volume":"8","author":"Ramos","year":"2025","journal-title":"Curr. Res. Microb. Sci."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.ab.2012.11.007","article-title":"Correction factors for membrane protein molecular weight readouts on sodium dodecyl sulfate-polyacrylamide gel electrophoresis","volume":"434","author":"Rath","year":"2013","journal-title":"Anal. Biochem."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/j.jmb.2018.01.005","article-title":"Molecular basis of substrate polyspecificity of the Candida albicans Mdr1p multidrug\/H(+) antiporter","volume":"430","author":"Redhu","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"3127","DOI":"10.1042\/BCJ20160407","article-title":"pHluorin enables insights into the transport mechanism of antiporter Mdr1: R215 is critical for drug\/H+ antiport","volume":"473","author":"Redhu","year":"","journal-title":"Biochem. J."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"fow043","DOI":"10.1093\/femsyr\/fow043","article-title":"MFS transporters of Candida species and their role in clinical drug resistance","volume":"16","author":"Redhu","year":"","journal-title":"FEMS Yeast Res."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/s41426-018-0045-x","article-title":"Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris","volume":"7","author":"Rhodes","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/1567-1364.12013","article-title":"Role of the yeast multidrug transporter Qdr2 in cation homeostasis and the oxidative stress response","volume":"13","author":"R\u00edos","year":"2013","journal-title":"FEMS Yeast Res."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"102208","DOI":"10.1016\/j.mib.2022.102208","article-title":"The molecular and genetic basis of antifungal resistance in the emerging fungal pathogen Candida auris","volume":"70","author":"Rybak","year":"2022","journal-title":"Curr. Opin. Microbiol."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"e1011066","DOI":"10.1371\/JOURNAL.PPAT.1011066","article-title":"The fungal expel of 5-fluorocytosine derived fluoropyrimidines mitigates its antifungal activity and generates a cytotoxic environment","volume":"18","author":"Sastr\u00e9-Vel\u00e1squez","year":"2022","journal-title":"PLoS Pathog."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1042\/BJ20140010","article-title":"Novel role of a family of major facilitator transporters in biofilm development and virulence of Candida albicans","volume":"460","author":"Shah","year":"2014","journal-title":"Biochem. J."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"538","DOI":"10.3390\/JOF8050538","article-title":"Spontaneous suppressors against debilitating transmembrane mutants of CaMdr1 disclose novel interdomain communication via signature motifs of the major facilitator superfamily","volume":"8","author":"Sharma","year":"2022","journal-title":"J. Fungi"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"e0227621","DOI":"10.1128\/aac.02276-21","article-title":"Comparative transcriptomics reveal possible mechanisms of amphotericin B resistance in Candida auris","volume":"66","author":"Shivarathri","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"100658","DOI":"10.1016\/j.lanepe.2023.100658","article-title":"The silent flucytosine shortage in Europe \u2013 not a distant problem","volume":"30","author":"Sprute","year":"2023","journal-title":"Lancet Reg. Heal. Eur."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"5931","DOI":"10.1128\/AAC.01504-13","article-title":"Multidrug-resistant transporter mdr1p-mediated uptake of a novel antifungal compound","volume":"57","author":"Sun","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"100878","DOI":"10.1016\/S2666-5247(24)00101-0","article-title":"Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study","volume":"5","author":"Suphavilai","year":"2024","journal-title":"Lancet Microbe"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"102947","DOI":"10.1016\/j.jiph.2025.102947","article-title":"Forty years of global research on WHO\u2019S four critical priority fungal pathogens: advances and prospects","volume":"18","author":"Tan","year":"2025","journal-title":"J. Infect. Public Health"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1006\/bbrc.2002.6703","article-title":"AQR1 gene (ORF YNL065w) encodes a plasma membrane transporter of the major facilitator superfamily that confers resistance to short-chain monocarboxylic acids and quinidine in Saccharomyces cerevisiae","volume":"292","author":"Tenreiro","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"168","DOI":"10.3390\/jof9020168","article-title":"Functional expression of recombinant Candida auris proteins in Saccharomyces cerevisiae enables azole susceptibility evaluation and drug discovery","volume":"9","author":"Toepfer","year":"","journal-title":"J. Fungi"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"663","DOI":"10.3390\/JOF9060663","article-title":"Clorgyline analogs synergize with azoles against drug efflux in Candida auris","volume":"9","author":"Toepfer","year":"","journal-title":"J. Fungi"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"3065","DOI":"10.1093\/JAC\/DKAF343","article-title":"Multidrug efflux pumps and innate azole resistance of Mucor lusitanicus","volume":"80","author":"Toepfer","year":"2025","journal-title":"J. Antimicrob. Chemother."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"W232","DOI":"10.1093\/NAR\/GKW256","article-title":"W-IQ-TREE: a fast online phylogenetic tool for maximum likelihood analysis","volume":"44","author":"Trifinopoulos","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1128\/EC.00290-06","article-title":"Saccharomyces cerevisiae multidrug resistance transporter Qdr2 is implicated in potassium uptake, providing a physiological advantage to quinidine-stressed cells","volume":"6","author":"Vargas","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1128\/AAC.48.7.2531-2537.2004","article-title":"Saccharomyces cerevisiae multidrug transporter Qdr2p (Yil121wp): localization and function as a quinidine resistance determinant","volume":"48","author":"Vargas","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"ofae072","DOI":"10.1093\/OFID\/OFAE072","article-title":"Optimizing the treatment of invasive candidiasis\u2014a case for combination therapy","volume":"11","author":"Wake","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1093\/bioinformatics\/btp033","article-title":"Jalview version 2\u2014a multiple sequence alignment editor and analysis workbench","volume":"25","author":"Waterhouse","year":"2009","journal-title":"Bioinformatics"},{"key":"ref79","volume-title":"Fungal Priority Pathogens List to Guide Research, Development and Public Health Action","year":"2022"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/s41467-025-67127-3","article-title":"Benchmarking all-atom biomolecular structure prediction with FoldBench","volume":"17","author":"Xu","year":"2025","journal-title":"Nat. Commun."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"foaf012","DOI":"10.1093\/FEMSYR\/FOAF012","article-title":"Functional analysis of Candida albicans Cdr1 through homologous and heterologous expression studies","volume":"25","author":"Zhao","year":"2025","journal-title":"FEMS Yeast Res."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"e01503-19","DOI":"10.1128\/JCM.01503-19","article-title":"Laboratory analysis of an outbreak of Candida auris in New York from 2016 to 2018: impact and lessons learned","volume":"58","author":"Zhu","year":"2020","journal-title":"J. Clin. Microbiol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1806653\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:51:47Z","timestamp":1778219507000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1806653\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":80,"alternative-id":["10.3389\/fmicb.2026.1806653"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1806653","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]},"article-number":"1806653"}}