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Updated: Jan 17, 2026
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Published on: December 28, 2017
Acquired amphotericin B resistance attributed to a mutated ERG3 in Candidozyma auris
Lauryn Massic1,2, Laura A Doorley3, Sarah J Jones3
1Nevada State Public Health Laboratory, Reno, Nevada, USA.
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.
Insights
A frameshift mutation in ERG3 significantly contributes to amphotericin B resistance in Candida auris, an emerging multidrug-resistant fungus. This study advances understanding of antifungal resistance mechanisms in this pathogen.
Area of Science:
- Mycology
- Infectious Diseases
- Genetics
Background:
- Candida auris is an emerging multidrug-resistant fungus identified in 2009.
- It causes invasive infections with high mortality (30-60%).
- 30-50% of C. auris isolates exhibit intrinsic resistance to amphotericin B.
Purpose of the Study:
- To characterize a clinical case of acquired amphotericin B resistance in C. auris.
- To identify the genetic mechanisms underlying this resistance.
- To understand the impact of ergosterol pathway alterations on C. auris.
Main Methods:
- Whole-genome sequencing
- Large-scale phenotypic screening
- Sterol profiling
- CRISPR-mediated genotypic reversion
Main Results:
- A frameshift deletion in ERG3 was identified as a major contributor to amphotericin B resistance.
- A nonsense mutation in ERG4 showed a modest contribution to resistance.
- Abrogation of ergosterol production led to a fitness cost and replacement with other sterols.
Conclusions:
- Acquired amphotericin B resistance in C. auris can be driven by mutations in the ergosterol biosynthesis pathway, specifically ERG3.
- Understanding these resistance mechanisms is crucial for managing C. auris infections.
- This study provides key insights into antifungal resistance in a critical fungal pathogen.
