Impact of Erg11 Amino Acid Substitutions Identified in Candida auris Clade III Isolates on Triazole Drug Susceptibility

耳念珠菌分支 III 分离株中鉴定的 Erg11 氨基酸取代对三唑类药物敏感性的影响

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作者:Benjamin Williamson, Adam Wilk, Kevin D Guerrero, Timothy D Mikulski, Tony N Elias, Indira Sawh, Geselle Cancino-Prado, Dianne Gardam, Christopher H Heath, Nelesh P Govender, David S Perlin, Milena Kordalewska, Kelley R Healey

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 the long-tailed triazoles posaconazole and itraconazole for the V125A/F126L, F126L, Y132F, and K143R alleles.

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