Novel Non-Hot Spot Modification in Fks1 of Candida auris Confers Echinocandin Resistance

Antimicrob Agents Chemother. 2023 Jun 15;67(6):e0042323. doi: 10.1128/aac.00423-23. Epub 2023 May 24.

Abstract

We determined the echinocandin susceptibility and FKS1 genotypes of 13 clinical isolates of Candida auris that were recovered from 4 patients at a tertiary care center in Salvador, Brazil. Three isolates were categorized as echinocandin-resistant, and they harbored a novel FKS1 mutation that led to an amino acid change W691L located downstream from hot spot 1. When introduced to echinocandin-susceptible C. auris strains by CRISPR/Cas9, Fks1 W691L induced elevated MIC values to all echinocandins (anidulafungin, 16 to 32×; caspofungin, >64×; micafungin, >64×).

Keywords: Candida; Candida auris; FKS1; anidulafungin; antifungal resistance; antifungal susceptibility testing; caspofungin; echinocandin resistance; echinocandins; micafungin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents* / pharmacology
  • Candida auris*
  • Caspofungin
  • Drug Resistance, Fungal / genetics
  • Echinocandins / pharmacology
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Humans
  • Microbial Sensitivity Tests

Substances

  • Antifungal Agents
  • Fungal Proteins
  • Echinocandins
  • Caspofungin