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

被引：12

作者：

Williamson, Benjamin ^{[1
]}

Wilk, Adam ^{[1
]}

Guerrero, Kevin D. ^{[2
]}

Mikulski, Timothy D. ^{[2
]}

Elias, Tony N. ^{[2
]}

Sawh, Indira ^{[1
]}

Cancino-Prado, Geselle ^{[1
]}

Gardam, Dianne ^{[3
]}

Heath, Christopher H. ^{[3
,4
,5
,6
]}

Govender, Nelesh P. ^{[7
,8
,9
]}

Perlin, David S. ^{[2
]}

Kordalewska, Milena ^{[2
]}

Healey, Kelley R. ^{[1
]}

机构：

[1] William Paterson Univ, Dept Biol, Wayne, NJ 07470 USA

[2] Hackensack Meridian Hlth, Ctr Discovery & Innovat, Nutley, NJ 07110 USA

[3] Fiona Stanley Hosp, Dept Microbiol, PathWest Lab Med FSH Network, Murdoch, WA, Australia

[4] Fiona Stanley Hosp, Dept Infect Dis, Murdoch, WA, Australia

[5] Royal Perth Hosp, Infect Dis, Perth, WA, Australia

[6] Univ Western Australia, Fac Hlth & Med Sci, Crawley, WA, Australia

[7] Natl Inst Communicable Dis, Ctr Healthcare Associated Infect Antimicrobial Re, Johannesburg, South Africa

[8] Univ Witwatersrand, Fac Hlth Sci, Sch Pathol, Parktown, South Africa

[9] Univ Exeter, MRC Ctr Med Mycol, Exeter, Devon, England

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2022年 / 66卷 / 01期

关键词：

Candida auris; ERG11; azole resistance; fluconazole resistance; clade III; African clade; heterologous expression; mutagenesis; short and long-tailed triazoles; AZOLE RESISTANCE; MUTATIONS;

D O I：

10.1128/AAC.01624-21

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页数：6

共 25 条

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Rybak, Jeffrey M.
Sharma, Cheshta
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Barker, Katherine S.
Palmer, Glen E.
Rogers, P. David
MICROBIOLOGY SPECTRUM, 2021, 9 (03):
[2] Limited ERG11 Mutations Identified in Isolates of Candida au ris Directly Contribute to Reduced Azole Susceptibility
Healey, Kelley R.
Kordalewska, Milena
Ortigosa, Cristina Jimenez
Singh, Ashutosh
Berrio, Indira
Chowdhary, Anuradha
Perlin, David S.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2018, 62 (10)
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Morio, Florent
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DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 2010, 66 (04) : 373 - 384
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Folia Microbiologica, 2010, 55 : 301 - 304
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Lee, M. -K.
FOLIA MICROBIOLOGICA, 2010, 55 (03) : 301 - 304
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DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 2013, 77 (04) : 327 - 329
[8] ERG11 gene polymorphisms and susceptibility to fluconazole in Candida isolates from diabetic and kidney transplant patients
Benedetti, Volmir Pitt
Savi, Daiani Cristina
Aluizio, Rodrigo
Adamoski, Douglas
Kava, Vanessa
Galli-Terasawa, Lygia Vitoria
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REVISTA DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL, 2019, 52
[9] Nucleotide substitutions in the Candida albicans ERG11 gene of azole-susceptible and azole-resistant clinical isolates
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ACTA BIOCHIMICA POLONICA, 2013, 60 (04) : 547 - 552
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Doorley, Laura A.
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Rybak, Jeffrey M.
Rogers, P. David
CLINICAL MICROBIOLOGY AND INFECTION, 2023, 29 (12)

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