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

Milena Kordalewska; Geselle Cancino-Prado; João Nobrega de Almeida; Igor Brasil Brandão; Renata Tigulini de Souza Peral; Arnaldo L. Colombo; David S. Perlin

doi:10.1128/aac.00423-23

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

Milena Kordalewska
, Geselle Cancino-Prado
, João Nobrega de Almeida
, Igor Brasil Brandão
, Renata Tigulini de Souza Peral
, Arnaldo L. Colombo
, David S. Perlin

Center for Discovery and Innovation

Hackensack Meridian Health
Universidade Federal de São Paulo
Hospital Israelita Albert Einstein
Hospital da Bahia
Ministério da Saúde do Brasil

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

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×).

Original language	English
Journal	Antimicrobial Agents and Chemotherapy
Volume	67
Issue number	6
DOIs	https://doi.org/10.1128/aac.00423-23
State	Published - Jun 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Candida
Candida auris
FKS1
anidulafungin
antifungal resistance
antifungal susceptibility testing
caspofungin
echinocandin resistance
echinocandins
micafungin

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10.1128/aac.00423-23

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@article{2dcda438e73042bda6ce6c20e0675926,

title = "Novel Non-Hot Spot Modification in Fks1 of Candida auris Confers Echinocandin Resistance",

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{\texttimes}; caspofungin, 64{\texttimes}; micafungin, 64{\texttimes}).",

keywords = "Candida, Candida auris, FKS1, anidulafungin, antifungal resistance, antifungal susceptibility testing, caspofungin, echinocandin resistance, echinocandins, micafungin",

author = "Milena Kordalewska and Geselle Cancino-Prado and \{de Almeida\}, \{Jo{\~a}o Nobrega\} and Brand{\~a}o, \{Igor Brasil\} and \{de Souza Peral\}, \{Renata Tigulini\} and Colombo, \{Arnaldo L.\} and Perlin, \{David S.\}",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 Kordalewska et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.",

year = "2023",

month = jun,

doi = "10.1128/aac.00423-23",

language = "English",

volume = "67",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

number = "6",

}

TY - JOUR

T1 - Novel Non-Hot Spot Modification in Fks1 of Candida auris Confers Echinocandin Resistance

AU - Kordalewska, Milena

AU - Cancino-Prado, Geselle

AU - de Almeida, João Nobrega

AU - Brandão, Igor Brasil

AU - de Souza Peral, Renata Tigulini

AU - Colombo, Arnaldo L.

AU - Perlin, David S.

PY - 2023/6

Y1 - 2023/6

N2 - 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×).

AB - 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×).

KW - Candida

KW - Candida auris

KW - FKS1

KW - anidulafungin

KW - antifungal resistance

KW - antifungal susceptibility testing

KW - caspofungin

KW - echinocandin resistance

KW - echinocandins

KW - micafungin

UR - https://www.scopus.com/pages/publications/85163715494

U2 - 10.1128/aac.00423-23

DO - 10.1128/aac.00423-23

M3 - Article

C2 - 37222585

AN - SCOPUS:85163715494

SN - 0066-4804

VL - 67

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 6

ER -

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

Abstract

UN SDGs

Keywords

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