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bioRxiv · 10.1101/2021.08.16.456589

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.
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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.

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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.. 2021-08-17. Impact of Erg11 amino acid substitutions identified in Candida auris clade III isolates on triazole drug susceptibility. https://doi.org/10.1101/2021.08.16.456589

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