Echinocandin Resistance in Candida auris Occurs in the Murine Gastrointestinal Tract Due to FKS1 Mutations

Antimicrob Agents Chemother. 2023 Apr 18;67(4):e0124322. doi: 10.1128/aac.01243-22. Epub 2023 Mar 15.

Abstract

Candida auris is resistant to multiple antifungal agents. This study investigated its antifungal susceptibility and explored FKS1 mutations across the isolates from mice enterically colonized with wild-type C. auris and treated with echinocandin. Resistant C. auris with FKS1 mutations, including S639F, S639Y, D642Y, R1354H, or R1354Y, were isolated and found to be micafungin- and caspofungin-resistant in vivo; however, the MICs of isolates with mutation in R1354 remained below the micafungin breakpoint in vitro.

Keywords: Candida auris; FKS1; antifungal resistance; echinocandins; gastrointestinal tract; yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • Candida auris*
  • Drug Resistance, Fungal / genetics
  • Echinocandins* / genetics
  • Echinocandins* / pharmacology
  • Fungal Proteins* / genetics
  • Gastrointestinal Tract
  • Glucosyltransferases*
  • Micafungin / pharmacology
  • Mice
  • Microbial Sensitivity Tests
  • Mutation / genetics

Substances

  • 1,3-beta-glucan synthase
  • Antifungal Agents
  • Echinocandins
  • Micafungin
  • Fks1 protein, Candida auris
  • Fungal Proteins
  • Glucosyltransferases