{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:25:04Z","timestamp":1792607104830,"version":"4.5.0"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"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":[[2024,10,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The global epidemic of drug-resistant\n              <jats:italic>Candida auris<\/jats:italic>\n              continues unabated. The initial report on pan-drug resistant (PDR)\n              <jats:italic>C. auris<\/jats:italic>\n              strains in a hospitalized patient in New York was unprecedented. PDR\n              <jats:italic>C. auris<\/jats:italic>\n              showed both known and unique mutations in the prominent gene targets of azoles, amphotericin B, echinocandins, and flucytosine. However, the factors that allow\n              <jats:italic>C. auris<\/jats:italic>\n              to acquire pan-drug resistance are not known. Therefore, we conducted a genomic, transcriptomic, and phenomic analysis to better understand PDR\n              <jats:italic>C. auris<\/jats:italic>\n              . Among 1,570 genetic variants in drug-resistant\n              <jats:italic>C. auris<\/jats:italic>\n              , 299 were unique to PDR strains. The whole-genome sequencing results suggested perturbations in genes associated with nucleotide biosynthesis, mRNA processing, and nuclear export of mRNA. Whole transcriptome sequencing of PDR\n              <jats:italic>C. auris<\/jats:italic>\n              revealed two genes to be significantly differentially expressed\u2014a DNA repair protein and DNA replication-dependent chromatin assembly factor 1. Of 59 novel transcripts, 12 transcripts had no known homology. We observed no fitness defects among multi-drug resistant (MDR) and PDR\n              <jats:italic>C. auris<\/jats:italic>\n              strains grown in nutrient-deficient or -enriched media at different temperatures. Phenotypic profiling revealed wider adaptability to nitrogenous nutrients and increased utilization of substrates critical in upper glycolysis and tricarboxylic acid cycle. Structural modeling of a 33-amino acid deletion in the gene for uracil phosphoribosyl transferase suggested an alternate route in\n              <jats:italic>C. auris<\/jats:italic>\n              to generate uracil monophosphate that does not accommodate 5-fluorouracil as a substrate. Overall, we find evidence of metabolic adaptations in MDR and PDR\n              <jats:italic>C. auris<\/jats:italic>\n              in response to antifungal drug lethality without deleterious fitness costs.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00911-24","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T13:02:42Z","timestamp":1726750962000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["What makes\n            <i>Candida auris<\/i>\n            pan-drug resistant? Integrative insights from genomic, transcriptomic, and phenomic analysis of clinical strains resistant to all four major classes of antifungal drugs"],"prefix":"10.1128","volume":"68","author":[{"given":"Johanna","family":"Rhodes","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Radboudumc, Nijmegen, the Netherlands"},{"name":"MRC GIDA, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5608-4256","authenticated-orcid":false,"given":"Jonathan","family":"Jacobs","sequence":"additional","affiliation":[{"name":"American Type Culture Collection, University Blvd, Manassas, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7928-9705","authenticated-orcid":false,"given":"Emily K.","family":"Dennis","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health, Albany, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati R.","family":"Manjari","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health, Albany, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh K.","family":"Banavali","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health, Albany, New York, USA"},{"name":"School of Public Health, University of Albany, Albany, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Marlow","sequence":"additional","affiliation":[{"name":"American Type Culture Collection, University Blvd, Manassas, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Anower","family":"Rokebul","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health, Albany, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0906-8426","authenticated-orcid":false,"given":"Sudha","family":"Chaturvedi","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health, Albany, New York, USA"},{"name":"School of Public Health, University of Albany, Albany, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3922-9676","authenticated-orcid":false,"given":"Vishnu","family":"Chaturvedi","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health, Albany, New York, USA"},{"name":"Westchester Medical Center\/New York Medical College, Valhalla, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.2008.00083.x"},{"key":"e_1_3_4_4_2","unstructured":"WHO. 2022. 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