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Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species

The azoles are the class of medications most commonly used to fight infections caused by Candida sp. Typically, resistance can be attributed to mutations in ERG11 gene (CYP51) which encodes the cytochrome P450 14α-demethylase, the primary target for the activity of azoles. The objective of this stud...

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Autores principales: Silva, Danielly Beraldo dos Santos, Rodrigues, Luana Mireli Carbonera, de Almeida, Adriana Araújo, de Oliveira, Kelly Mari Pires, Grisolia/, Alexéia Barufatti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Instituto Oswaldo Cruz, Ministério da Saúde 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804502/
https://www.ncbi.nlm.nih.gov/pubmed/26982177
http://dx.doi.org/10.1590/0074-02760150400
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author Silva, Danielly Beraldo dos Santos
Rodrigues, Luana Mireli Carbonera
de Almeida, Adriana Araújo
de Oliveira, Kelly Mari Pires
Grisolia/, Alexéia Barufatti
author_facet Silva, Danielly Beraldo dos Santos
Rodrigues, Luana Mireli Carbonera
de Almeida, Adriana Araújo
de Oliveira, Kelly Mari Pires
Grisolia/, Alexéia Barufatti
author_sort Silva, Danielly Beraldo dos Santos
collection PubMed
description The azoles are the class of medications most commonly used to fight infections caused by Candida sp. Typically, resistance can be attributed to mutations in ERG11 gene (CYP51) which encodes the cytochrome P450 14α-demethylase, the primary target for the activity of azoles. The objective of this study was to identify mutations in the coding region of theERG11 gene in clinical isolates of Candidaspecies known to be resistant to azoles. We identified three new synonymous mutations in the ERG11 gene in the isolates of Candida glabrata (C108G, C423T and A1581G) and two new nonsynonymous mutations in the isolates of Candida krusei - A497C (Y166S) and G1570A (G524R). The functional consequence of these nonsynonymous mutations was predicted using evolutionary conservation scores. The G524R mutation did not have effect on 14α-demethylase functionality, while the Y166S mutation was found to affect the enzyme. This observation suggests a possible link between the mutation and dose-dependent sensitivity to voriconazole in the clinical isolate of C. krusei. Although the presence of the Y166S in phenotype of reduced azole sensitivity observed in isolate C. kruseidemands investigation, it might contribute to the search of new therapeutic agents against resistant Candida isolates.
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spelling pubmed-48045022016-03-23 Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species Silva, Danielly Beraldo dos Santos Rodrigues, Luana Mireli Carbonera de Almeida, Adriana Araújo de Oliveira, Kelly Mari Pires Grisolia/, Alexéia Barufatti Mem Inst Oswaldo Cruz Articles The azoles are the class of medications most commonly used to fight infections caused by Candida sp. Typically, resistance can be attributed to mutations in ERG11 gene (CYP51) which encodes the cytochrome P450 14α-demethylase, the primary target for the activity of azoles. The objective of this study was to identify mutations in the coding region of theERG11 gene in clinical isolates of Candidaspecies known to be resistant to azoles. We identified three new synonymous mutations in the ERG11 gene in the isolates of Candida glabrata (C108G, C423T and A1581G) and two new nonsynonymous mutations in the isolates of Candida krusei - A497C (Y166S) and G1570A (G524R). The functional consequence of these nonsynonymous mutations was predicted using evolutionary conservation scores. The G524R mutation did not have effect on 14α-demethylase functionality, while the Y166S mutation was found to affect the enzyme. This observation suggests a possible link between the mutation and dose-dependent sensitivity to voriconazole in the clinical isolate of C. krusei. Although the presence of the Y166S in phenotype of reduced azole sensitivity observed in isolate C. kruseidemands investigation, it might contribute to the search of new therapeutic agents against resistant Candida isolates. Instituto Oswaldo Cruz, Ministério da Saúde 2016-03 /pmc/articles/PMC4804502/ /pubmed/26982177 http://dx.doi.org/10.1590/0074-02760150400 Text en http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Silva, Danielly Beraldo dos Santos
Rodrigues, Luana Mireli Carbonera
de Almeida, Adriana Araújo
de Oliveira, Kelly Mari Pires
Grisolia/, Alexéia Barufatti
Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species
title Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species
title_full Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species
title_fullStr Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species
title_full_unstemmed Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species
title_short Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species
title_sort novel point mutations in the erg11 gene in clinical isolates of azole resistant candida species
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804502/
https://www.ncbi.nlm.nih.gov/pubmed/26982177
http://dx.doi.org/10.1590/0074-02760150400
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