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

Massic, Lauryn, Doorley, Laura A., Jones, Sarah J., Richardson, Irene, Siao, Danielle Denise, Siao, Lauren, Dykema, Philip, Hua, Chi, Schneider, Emily, Cuomo, Christina A., Rogers, P. David, Van Hooser, Stephanie, Parker, Josie E., Kelly, Steven L., Hess, David, Rybak, Jeffrey M. and Pandori, Mark 2025. Acquired amphotericin B resistance attributed to a mutated ERG3 in Candidozyma auris. Antimicrobial Agents and Chemotherapy , e00601-25. 10.1128/aac.00601-25

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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.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Biosciences
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Start Date: 2025-09-22
Publisher:	American Society for Microbiology
ISSN:	0066-4804
Date of First Compliant Deposit:	9 October 2025
Date of Acceptance:	19 August 2025
Last Modified:	09 Oct 2025 08:30
URI:	https://orca.cardiff.ac.uk/id/eprint/181566

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