{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T18:52:49Z","timestamp":1793904769170,"version":"4.8.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Candida auris<\/jats:italic>\n                      has emerged as a fungal pathogen of particular concern owing in part to its propensity to exhibit antifungal resistance, especially to the commonly prescribed antifungal fluconazole. A mutation in\n                      <jats:italic toggle=\"yes\">TAC1B<\/jats:italic>\n                      , which encodes a zinc cluster transcription factor, has been shown to confer increased resistance to fluconazole. In this work, we aimed to determine how mutations in\n                      <jats:italic toggle=\"yes\">TAC1B<\/jats:italic>\n                      exert this effect.\n                      <jats:italic toggle=\"yes\">TAC1B<\/jats:italic>\n                      mutations leading to A640V, A657V, and F862_N866del, found in fluconazole-resistant clinical isolates, were introduced into two susceptible Clade I backgrounds using CRISPR-Cas9 gene editing. These\n                      <jats:italic toggle=\"yes\">TAC1B<\/jats:italic>\n                      mutations conferred increased fluconazole resistance, as well as increased resistance to other triazoles as measured by broth microdilution. RNA-seq revealed that the ATP-binding cassette (ABC) transporter gene\n                      <jats:italic toggle=\"yes\">CDR1<\/jats:italic>\n                      as well as the major facilitator superfamily (MFS) transporter gene\n                      <jats:italic toggle=\"yes\">MDR1<\/jats:italic>\n                      were both upregulated in the presence of these\n                      <jats:italic toggle=\"yes\">TAC1B<\/jats:italic>\n                      mutations. Disruption of\n                      <jats:italic toggle=\"yes\">CDR1<\/jats:italic>\n                      increased susceptibility in strains with\n                      <jats:italic toggle=\"yes\">TAC1B<\/jats:italic>\n                      mutations, whereas disruption of\n                      <jats:italic toggle=\"yes\">MDR1<\/jats:italic>\n                      had little to no effect. However, disruption of both\n                      <jats:italic toggle=\"yes\">CDR1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">MDR1<\/jats:italic>\n                      resulted in an additional increase in susceptibility as compared with disruption of\n                      <jats:italic toggle=\"yes\">CDR1<\/jats:italic>\n                      alone.\n                      <jats:italic toggle=\"yes\">TAC1B<\/jats:italic>\n                      mutations, leading to A640V, A657V, and F862_N866del all result in increased resistance to fluconazole and other triazole antifungals and increased expression of both\n                      <jats:italic toggle=\"yes\">CDR1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">MDR1<\/jats:italic>\n                      in\n                      <jats:italic toggle=\"yes\">C. auris<\/jats:italic>\n                      . Together, these data suggest\n                      <jats:italic toggle=\"yes\">CDR1<\/jats:italic>\n                      is the primary driver of resistance conferred by these\n                      <jats:italic toggle=\"yes\">TAC1B<\/jats:italic>\n                      mutations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00300-25","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T15:39:09Z","timestamp":1755531549000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Mutations in\n                    <i>TAC1B<\/i>\n                    drive increased\n                    <i>CDR1<\/i>\n                    and\n                    <i>MDR1<\/i>\n                    expression and azole resistance in\n                    <i>Candida auris<\/i>"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3824-6829","authenticated-orcid":false,"given":"Katherine S.","family":"Barker","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r3e0967","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darian J.","family":"Santana","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r3e0967","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r3e0967","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy L.","family":"Peters","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r3e0967","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Rybak","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r3e0967","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4227-8687","authenticated-orcid":true,"given":"Joachim","family":"Morschh\u00e4user","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00fbnyb24","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Molecular Infection Biology, University of W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina A.","family":"Cuomo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05gq02987","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Brown University","place":["Providence, USA"]},{"id":[{"id":"https:\/\/ror.org\/05a0ya142","id-type":"ROR","asserted-by":"publisher"}],"name":"Broad Institute","place":["Cambridge, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4401-0679","authenticated-orcid":true,"given":"P. David","family":"Rogers","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r3e0967","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-023-00960-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.7326\/M22-3469"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2022.102208"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6901a2"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1272"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-145-10-2701"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.6.1639-1652.2004"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00103-08"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030164"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-5793(97)00785-0"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/Spectrum.01585-21"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00067-22"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00057-19"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00365-20"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/myc.13022"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0061(19980430)14:6<517::AID-YEA250>3.0.CO;2-D"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00327-07"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00279-20"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1807698115"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00289-22"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1101\/2025.03.31.646430"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27545-5"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adf8972"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00125-19"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-024-01854-z"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky379"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw924"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-2-r14"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx364"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00421"}],"updated-by":[{"DOI":"10.1128\/aac.01507-25","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000}}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00300-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00300-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T13:02:47Z","timestamp":1759323767000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00300-25"}},"subtitle":[],"editor":[{"given":"Damian J.","family":"Krysan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":34,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1128\/aac.00300-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.00300-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2025-02-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00300-25"}}