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Acquired amphotericin B resistance attributed to a mutated ERG3 in Candidozyma auris

Year: 2025
Type: article
Abstract: ABSTRACT First identified in 2009, Candidozyma auris (formerly Candida auris ) is an emerging multidrug-resistant fungus that can cause invasive infections with a crude mortality rate ranging from 30 to 60%. Currently, 30–50% of C. auris isolates are intrinsically resistant to amphotericin B. In this study, we characterized a clinical case of acquired amphotericin B resistance using whole-genome sequencing, a large-scale phenotypic screen, comprehensive sterol profiling, and genotypic reversion using CRISPR. Data obtained in this study provide evidence that a deletion resulting in a frameshift in ERG3 significantly contributes to the observed resistant phenotype, and a nonsense mutation in ERG4 may more modestly contribute to resistance. Characterization of this isolate also revealed that a fitness cost is associated with the abrogation of ergosterol production and its replacement with other late-stage sterols. This article presents a clinical case description of amphotericin B resistance from a frameshift mutation in ERG3 in C. auris and marks an advancement in the understanding of antifungal resistance in this fungal pathogen.
DOI: 10.1128/aac.00601-25
Authors: Lauryn Massic, Laura A Doorley, Sarah J Jones, Irene Richardson, Danielle Denise Siao, Lauren Siao, Philip Dykema, Chi Hua, Emily Schneider, Christina A. Cuomo, P. David Rogers, Stephanie Van Hooser, Josie E Parker, Steven L Kelly, David Hess, Jeffrey M Rybak, Mark Pandori
Institutions: University of Nevada, Reno, St. Jude Children's Research Hospital, Washington State Department of Health, State of Washington, Broad Institute, Brown University, Cardiff University, Swansea University
Language: English
Field: Medicine
Open Access status: diamond
Funders: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, American Lebanese Syrian Associated Charities, Broad Institute, Instituto Nacional de Cancerología, Centers for Disease Control and Prevention, National Cancer Institute, National Institute of Allergy and Infectious Diseases
Awards: G10969003, G2067768121, G295163761, G3080508409, G5093948117, Cancer Center Support Grant (CCSG), Mapping the genomic and molecular mechanisms of antifungal resistance in the emerging fungal pathogen Candida auris
OpenAlex ID: W4414410283
FWCI: 9.879
Cites: 35
Cited by: 14
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