Impact of Erg11 Amino Acid Substitutions Identified in Candida auris Clade III Isolates on Triazole Drug Susceptibility

Benjamin Williamson; Adam Wilk; Kevin D. Guerrero; Timothy D. Mikulski; Tony N. Elias; Indira Sawh; Geselle Cancino-Prado; Dianne Gardam; Christopher H. Heath; Nelesh P. Govender; David S. Perlin; Milena Kordalewska; Kelley R. Healey

doi:10.1128/AAC.01624-21

Impact of Erg11 Amino Acid Substitutions Identified in Candida auris Clade III Isolates on Triazole Drug Susceptibility

Benjamin Williamson
, Adam Wilk
, Kevin D. Guerrero
, Timothy D. Mikulski
, Tony N. Elias
, Indira Sawh
, Geselle Cancino-Prado
, Dianne Gardam
, Christopher H. Heath
, Nelesh P. Govender
, David S. Perlin
, Milena Kordalewska
, Kelley R. Healey

Center for Discovery and Innovation

William Paterson University
Hackensack Meridian Health
Fiona Stanley Hospital
Royal Perth Hospital
University of Western Australia
National Health Laboratory Services
University of the Witwatersrand
University of Exeter

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

27 Scopus citations

Abstract

ERG11 sequencing of 28 Candida auris clade III isolates revealed the presence of concomitant V125A and F126L substitutions. Heterologous expression of Erg11-V125A/F126L in Saccharomyces cerevisiae led to reduced fluconazole and voriconazole susceptibilities. Generation of single substitution gene variants through site-directed mutagenesis uncovered that F126L primarily contributes to the elevated triazole MICs. A similar yet diminished pattern of reduced susceptibility was observed with the long-tailed triazoles posaconazole and itraconazole for the V125A/F126L, F126L, Y132F, and K143R alleles.

Original language	English
Article number	e01624-21
Journal	Antimicrobial Agents and Chemotherapy
Volume	66
Issue number	1
DOIs	https://doi.org/10.1128/AAC.01624-21
State	Published - Jan 2022

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

African clade
Azole resistance
Candida auris
Clade III
ERG11
Fluconazole resistance
Heterologous expression
Mutagenesis
Short- and long-tailed triazoles

Access to Document

10.1128/AAC.01624-21

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Williamson, B., Wilk, A., Guerrero, K. D., Mikulski, T. D., Elias, T. N., Sawh, I., Cancino-Prado, G., Gardam, D., Heath, C. H., Govender, N. P., Perlin, D. S., Kordalewska, M., & Healey, K. R. (2022). Impact of Erg11 Amino Acid Substitutions Identified in Candida auris Clade III Isolates on Triazole Drug Susceptibility. Antimicrobial Agents and Chemotherapy, 66(1), Article e01624-21. https://doi.org/10.1128/AAC.01624-21

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title = "Impact of Erg11 Amino Acid Substitutions Identified in Candida auris Clade III Isolates on Triazole Drug Susceptibility",

abstract = "ERG11 sequencing of 28 Candida auris clade III isolates revealed the presence of concomitant V125A and F126L substitutions. Heterologous expression of Erg11-V125A/F126L in Saccharomyces cerevisiae led to reduced fluconazole and voriconazole susceptibilities. Generation of single substitution gene variants through site-directed mutagenesis uncovered that F126L primarily contributes to the elevated triazole MICs. A similar yet diminished pattern of reduced susceptibility was observed with the long-tailed triazoles posaconazole and itraconazole for the V125A/F126L, F126L, Y132F, and K143R alleles.",

keywords = "African clade, Azole resistance, Candida auris, Clade III, ERG11, Fluconazole resistance, Heterologous expression, Mutagenesis, Short- and long-tailed triazoles",

author = "Benjamin Williamson and Adam Wilk and Guerrero, \{Kevin D.\} and Mikulski, \{Timothy D.\} and Elias, \{Tony N.\} and Indira Sawh and Geselle Cancino-Prado and Dianne Gardam and Heath, \{Christopher H.\} and Govender, \{Nelesh P.\} and Perlin, \{David S.\} and Milena Kordalewska and Healey, \{Kelley R.\}",

note = "Publisher Copyright: {\textcopyright} 2022 American Society for Microbiology.",

year = "2022",

month = jan,

doi = "10.1128/AAC.01624-21",

language = "English",

volume = "66",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

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Williamson, B, Wilk, A, Guerrero, KD, Mikulski, TD, Elias, TN, Sawh, I, Cancino-Prado, G, Gardam, D, Heath, CH, Govender, NP, Perlin, DS , Kordalewska, M & Healey, KR 2022, 'Impact of Erg11 Amino Acid Substitutions Identified in Candida auris Clade III Isolates on Triazole Drug Susceptibility', Antimicrobial Agents and Chemotherapy, vol. 66, no. 1, e01624-21. https://doi.org/10.1128/AAC.01624-21

TY - JOUR

T1 - Impact of Erg11 Amino Acid Substitutions Identified in Candida auris Clade III Isolates on Triazole Drug Susceptibility

AU - Williamson, Benjamin

AU - Wilk, Adam

AU - Guerrero, Kevin D.

AU - Mikulski, Timothy D.

AU - Elias, Tony N.

AU - Sawh, Indira

AU - Cancino-Prado, Geselle

AU - Gardam, Dianne

AU - Heath, Christopher H.

AU - Govender, Nelesh P.

AU - Perlin, David S.

AU - Kordalewska, Milena

AU - Healey, Kelley R.

PY - 2022/1

Y1 - 2022/1

N2 - ERG11 sequencing of 28 Candida auris clade III isolates revealed the presence of concomitant V125A and F126L substitutions. Heterologous expression of Erg11-V125A/F126L in Saccharomyces cerevisiae led to reduced fluconazole and voriconazole susceptibilities. Generation of single substitution gene variants through site-directed mutagenesis uncovered that F126L primarily contributes to the elevated triazole MICs. A similar yet diminished pattern of reduced susceptibility was observed with the long-tailed triazoles posaconazole and itraconazole for the V125A/F126L, F126L, Y132F, and K143R alleles.

AB - ERG11 sequencing of 28 Candida auris clade III isolates revealed the presence of concomitant V125A and F126L substitutions. Heterologous expression of Erg11-V125A/F126L in Saccharomyces cerevisiae led to reduced fluconazole and voriconazole susceptibilities. Generation of single substitution gene variants through site-directed mutagenesis uncovered that F126L primarily contributes to the elevated triazole MICs. A similar yet diminished pattern of reduced susceptibility was observed with the long-tailed triazoles posaconazole and itraconazole for the V125A/F126L, F126L, Y132F, and K143R alleles.

KW - African clade

KW - Azole resistance

KW - Candida auris

KW - Clade III

KW - ERG11

KW - Fluconazole resistance

KW - Heterologous expression

KW - Mutagenesis

KW - Short- and long-tailed triazoles

UR - https://www.scopus.com/pages/publications/85123081853

U2 - 10.1128/AAC.01624-21

DO - 10.1128/AAC.01624-21

M3 - Article

C2 - 34633842

AN - SCOPUS:85123081853

SN - 0066-4804

VL - 66

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 1

M1 - e01624-21

ER -

Impact of Erg11 Amino Acid Substitutions Identified in Candida auris Clade III Isolates on Triazole Drug Susceptibility

Abstract

UN SDGs

Keywords

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