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

Lauryn Massic Orcid Logo, Laura A. Doorley Orcid Logo, Sarah J. Jones, Irene Richardson, Danielle Denise Siao, Lauren Siao, Philip Dykema Orcid Logo, Chi Hua, Emily Schneider, Christina A. Cuomo, P. David Rogers Orcid Logo, Stephanie Van Hooser, Josie E. Parker Orcid Logo, Steven Kelly, David Hess, Jeffrey M. Rybak Orcid Logo, Mark Pandori Orcid Logo

Antimicrobial Agents and Chemotherapy, Start page: e00601-25

Swansea University Author: Steven Kelly

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DOI (Published version): 10.1128/aac.00601-25

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, w...

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Published in: Antimicrobial Agents and Chemotherapy
ISSN: 0066-4804 1098-6596
Published: American Society for Microbiology 2025
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URI: https://cronfa.swan.ac.uk/Record/cronfa70522
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.
Keywords: microbial, public health, genetics, ERG3, amphotericin B, multidrug resistance, Candida auris
College: Faculty of Medicine, Health and Life Sciences
Funders: This research was supported in part by the ALSAC and the National Cancer Institute grant P30 CA021765, NIH NIAID grant R01 AI169066 awarded to P.D.R. and C.A.C, NIAID grant U19AI110818 to the Broad Institute (C.A.C.), the St. Jude Children’s Research Hospital Children’s Infection Defense Center grant (J.M.R.), and the Society of Infectious Diseases Pharmacists Young Investigator Research Award granted to J.M.R. This publication was supported by the Nevada State Department of Health and Human Services through Grant # 5 NU50CK000560-05-00 from Epidemiology and Laboratory Capacity for Infectious Diseases (ELC), its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Department nor Epidemiology and Laboratory Capacity for Infectious Diseases (ELC).
Start Page: e00601-25

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