Massic, Lauryn, Doorley, Laura, Jones, Sarah, Richardson, Irene, Siao, Danielle, Siao, Lauren, Dykema, Philip, Hua, Chi, Schneider, Emily, Cuomo, Christina, Rogers, P., van Hooser, Stephanie, Parker, Josie, Kelly, Steven, Hess, David, Rybak, Jeffrey 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 |
| Publisher: | American Society for Microbiology |
| ISSN: | 0066-4804 |
| Date of First Compliant Deposit: | 21 August 2025 |
| Date of Acceptance: | 19 August 2025 |
| Last Modified: | 22 Oct 2025 14:00 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/180583 |
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