Acquired Amphotericin B Resistance Attributed to a Mutated ERG3 in Candidozyma auris

Massic, L. K.; Doorley, L. A.; Jones, S. J.; Richardson, I.; Siao, D. D.; Siao, L.; Dykema, P.; Hua, C. N.; Schneider, E.; Cuomo, C. A.; Rogers, P. D.; Van Hooser, S.; Parker, J.; Kelly, S. L.; Hess, D.; Rybak, J. M.; Pandori, M. W.

doi:10.1101/2025.03.30.646105

bioRxiv · 10.1101/2025.03.30.646105

Acquired Amphotericin B Resistance Attributed to a Mutated ERG3 in Candidozyma auris

Massic, L. K.·Doorley, L. A.·Jones, S. J.·Richardson, I.·Siao, D. D.·Siao, L.·Dykema, P.·Hua, C. N.·Schneider, E.·Cuomo, C. A.·Rogers, P. D.·Van Hooser, S.·Parker, J.·Kelly, S. L.·Hess, D.·Rybak, J. M.·Pandori, M. W.

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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 30-60%. Currently, 30-50% of C. auris isolates are intrinsically resistant to amphotericin B. In this work, 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 work provides evidence that a deletion resulting in a frameshift in ERG3 contributes to the observed resistant phenotype. Characterization of this isolate also revealed 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.

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Massic, L. K., Doorley, L. A., Jones, S. J., Richardson, I., Siao, D. D., Siao, L., Dykema, P., Hua, C. N., Schneider, E., Cuomo, C. A., Rogers, P. D., Van Hooser, S., Parker, J., Kelly, S. L., Hess, D., Rybak, J. M., Pandori, M. W.. 2025-04-03. Acquired Amphotericin B Resistance Attributed to a Mutated ERG3 in Candidozyma auris. https://doi.org/10.1101/2025.03.30.646105

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