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Updated: May 13, 2025

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
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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.

Biorxiv : the Preprint Server for Biology
|April 16, 2025
PubMed

Insights

Candida auris, a multidrug-resistant fungus, can develop resistance to amphotericin B. A frameshift mutation in the ERG3 gene was identified as a cause of this acquired resistance in a clinical case.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Antifungal Resistance

Background:

  • Candida auris is an emerging multidrug-resistant fungal pathogen.
  • It causes invasive infections with high mortality rates (30-60%).
  • Many C. auris isolates exhibit intrinsic resistance to amphotericin B (30-50%).

Purpose of the Study:

  • To characterize a clinical case of acquired amphotericin B resistance in Candida auris.
  • To investigate the genetic and molecular mechanisms underlying this resistance.

Main Methods:

  • Whole genome sequencing
  • Large-scale phenotypic screening
  • Sterol profiling
  • CRISPR-based genotypic reversion

Main Results:

  • A deletion causing a frameshift mutation in the ERG3 gene was identified.
  • This ERG3 mutation contributes to acquired amphotericin B resistance.
  • Ergosterol production abrogation and replacement with other sterols incur a fitness cost.

Conclusions:

  • A frameshift mutation in ERG3 is associated with acquired amphotericin B resistance in C. auris.
  • Understanding antifungal resistance mechanisms is crucial for managing C. auris infections.
  • This study advances knowledge of antifungal resistance in this critical fungal pathogen.

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