Published on Tue Aug 17 2021

Impact of Erg11 amino acid substitutions identified in Candida auris clade III isolates on triazole drug susceptibility

Williamson, B., Wilk, A., Guerrero, K. D., Mikulski, T. D., Elias, T. N., Sawh, I., Cancino-Prado, G., Gardam, D., Heath, C. H., Govender, N. P., Perlin, D. S., Kordalewska, M., Healey, K. R.

ERG11 sequencing of 28 Candida auris clade III isolates revealed the presence of concomitant V125A and F126L substitutions. Heterologous expression of Erg11-V125A/F126L in Saccharomyces cerevisiae led to

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Abstract

ERG11 sequencing of 28 Candida auris clade III isolates revealed the presence of concomitant V125A and F126L substitutions. Heterologous expression of Erg11-V125A/F126L in Saccharomyces cerevisiae led to reduced fluconazole and voriconazole susceptibilities. Generation of single substitution gene variants through site-directed mutagenesis uncovered that F126L primarily contributes to the elevated triazole MICs. A similar, yet diminished pattern of reduced susceptibility was observed with long-tailed triazoles posaconazole and itraconazole for V125A/F126L, F126L, Y132F, and K143R alleles.