Limited ERG11 Mutations Identified in Isolates of Candida auris Directly Contribute to Reduced Azole Susceptibility.

Kelley R Healey,David S Perlin,Cristina Jiménez Ortigosa,Anuradha Chowdhary,Ashutosh Singh,Indira Berrío,Milena Kordalewska

doi:10.1128/aac.01427-18

Abstract

Multiple Erg11 amino acid substitutions were identified in clinical isolates of Candida auris originating from India and Colombia. Elevated azole MICs were detected in Saccharomyces cerevisiae upon heterologous expression of C. aurisERG11 alleles that encoded for Y132F or K143R substitutions; however, expression of alleles encoding I466M, Y501H, or other clade-defined amino acid differences yielded susceptible MICs. Similar to other Candida species, specific C. aurisERG11 mutations resulted directly in reduced azole susceptibility.

Highlights

The emerging pathogen Candida auris has spread across the globe, caused hospital outbreaks, and been reported as refractory to common antifungal agents, including triazoles, such as fluconazole and voriconazole
Chowdhary and colleagues [6] recently identified Erg11 amino acid substitutions Y132F and K143R in 100% (34/34) of C. auris isolates from India that demonstrated elevated fluconazole MICs (32 to Ն64 ␮g/ml)
The equivalent Y132F and/or K143R substitutions were associated with azole resistance in Candida tropicalis [12,13,14], Candida parapsilosis [15, 16], and Candida orthopsilosis [17]

Summary

Introduction

The emerging pathogen Candida auris has spread across the globe, caused hospital outbreaks, and been reported as refractory to common antifungal agents, including triazoles, such as fluconazole and voriconazole. Chowdhary and colleagues [6] recently identified Erg11 amino acid substitutions Y132F and K143R in 100% (34/34) of C. auris isolates from India that demonstrated elevated fluconazole MICs (32 to Ն64 ␮g/ml). A wild-type ERG11 genotype was reported in 4 of 5 isolates exhibiting low fluconazole MICs (1 to 2 ␮g/ml) [6].

Results

Conclusion