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

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

Milena Kordalewska  1 , Geselle Cancino-Prado  1 , João Nobrega de Almeida Júnior  2   3 , Igor Brasil Brandão  4 , Renata Tigulini de Souza Peral  5 , Arnaldo L Colombo  2 , David S Perlin  1
Affiliations

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

Milena Kordalewska et al. Antimicrob Agents Chemother. .

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.

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Conflict of interest statement

The authors declare a conflict of interest. A.L.C. serves on advisory boards/educational programs of Amgen, Ache, Biotoscana-United Medical, Eurofarma, Mundipharma, Gilead, and Pfizer. D.S.P. receives funding from the U.S. National Institutes of Health (NIH) and contracts with Merck, Regeneron and Pfizer. He serves on advisory boards for N8 Medical and Scynexis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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