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

Antimicrob Agents Chemother. 2022 Jan 18;66(1):e0162421. doi: 10.1128/AAC.01624-21. Epub 2021 Oct 11.

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.

Keywords: African clade; Candida auris; ERG11; azole resistance; clade III; fluconazole resistance; heterologous expression; mutagenesis; short- and long-tailed triazoles.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Substitution
  • Antifungal Agents / pharmacology
  • Candida auris* / drug effects
  • Candida auris* / genetics
  • Drug Resistance, Fungal* / genetics
  • Fluconazole / pharmacology
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Microbial Sensitivity Tests
  • Triazoles / pharmacology

Substances

  • Antifungal Agents
  • Fungal Proteins
  • Triazoles
  • Fluconazole