Molecular confirmation of the linkage between the rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistance

Autores
Macedo, Daiana; Leonardelli, Florencia; Dudiuk, Catiana Beatriz; Theill, Laura; Cabeza, Matías Sebastián; Gamarra, Soledad; Garcia, Guillermo Manuel
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Rhizopus oryzae is the most prevalent causative agent of mucormycosis, an increasingly reported opportunistic fungal infection. These Mucorales are intrinsically resistant to Candida- and Aspergillus-active antifungal azole drugs, such as fluconazole (FLC) and voriconazole, respectively. Despite its importance, the molecular mechanisms of its intrinsic azole resistance have not been elucidated yet. The aim of this work was to establish if the Rhizopus oryzae CYP51 genes are uniquely responsible for intrinsic voriconazole and fluconazole resistance in these fungal pathogens. Two CYP51 genes were identified in the R. oryzae genome. We classified them as CYP51A and CYP51B based on their sequence similarity with other known fungal CYP51 genes. Later, we obtained a chimeric Aspergillus fumigatus strain harboring a functional R. oryzae CYP51A gene expressed under the regulation of the wild-type A. fumigatus CYP51A promoter and terminator. The mutant was selected after transformation by using a novel procedure taking advantage of the FLC hypersusceptibility of the A. fumigatus CYP51A deletion mutant used as the recipient strain. The azole susceptibility patterns of the A. fumigatus transformants harboring R. oryzae CYP51A mimicked exactly the azole susceptibility patterns of this mucormycete. The data presented in this work demonstrate that the R. oryzae CYP51A coding sequence is uniquely responsible for the R. oryzae azole susceptibility patterns.
Fil: Macedo, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Unidad de Administración Territorial; Argentina
Fil: Leonardelli, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Unidad de Administración Territorial; Argentina
Fil: Dudiuk, Catiana Beatriz. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Fil: Theill, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Unidad de Administración Territorial; Argentina
Fil: Cabeza, Matías Sebastián. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Fil: Gamarra, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Unidad de Administración Territorial; Argentina
Fil: Garcia, Guillermo Manuel. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Materia
AZOLE
CYP51
FLUCONAZOLE
INTRINSIC RESISTANCE
MOLECULAR MECHANISM
MUCORALES
RESISTANCE
RHIZOPUS
VORICONAZOLE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/89630
Acceder
id CONICETDig_48f0b5dd80ce70512851de56124df0a3
oai_identifier_str oai:ri.conicet.gov.ar:11336/89630
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Molecular confirmation of the linkage between the rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistanceMacedo, DaianaLeonardelli, FlorenciaDudiuk, Catiana BeatrizTheill, LauraCabeza, Matías SebastiánGamarra, SoledadGarcia, Guillermo ManuelAZOLECYP51FLUCONAZOLEINTRINSIC RESISTANCEMOLECULAR MECHANISMMUCORALESRESISTANCERHIZOPUSVORICONAZOLEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Rhizopus oryzae is the most prevalent causative agent of mucormycosis, an increasingly reported opportunistic fungal infection. These Mucorales are intrinsically resistant to Candida- and Aspergillus-active antifungal azole drugs, such as fluconazole (FLC) and voriconazole, respectively. Despite its importance, the molecular mechanisms of its intrinsic azole resistance have not been elucidated yet. The aim of this work was to establish if the Rhizopus oryzae CYP51 genes are uniquely responsible for intrinsic voriconazole and fluconazole resistance in these fungal pathogens. Two CYP51 genes were identified in the R. oryzae genome. We classified them as CYP51A and CYP51B based on their sequence similarity with other known fungal CYP51 genes. Later, we obtained a chimeric Aspergillus fumigatus strain harboring a functional R. oryzae CYP51A gene expressed under the regulation of the wild-type A. fumigatus CYP51A promoter and terminator. The mutant was selected after transformation by using a novel procedure taking advantage of the FLC hypersusceptibility of the A. fumigatus CYP51A deletion mutant used as the recipient strain. The azole susceptibility patterns of the A. fumigatus transformants harboring R. oryzae CYP51A mimicked exactly the azole susceptibility patterns of this mucormycete. The data presented in this work demonstrate that the R. oryzae CYP51A coding sequence is uniquely responsible for the R. oryzae azole susceptibility patterns.Fil: Macedo, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Unidad de Administración Territorial; ArgentinaFil: Leonardelli, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Unidad de Administración Territorial; ArgentinaFil: Dudiuk, Catiana Beatriz. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Theill, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Unidad de Administración Territorial; ArgentinaFil: Cabeza, Matías Sebastián. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Gamarra, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Unidad de Administración Territorial; ArgentinaFil: Garcia, Guillermo Manuel. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaAmerican Society for Microbiology2018-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/89630Macedo, Daiana; Leonardelli, Florencia; Dudiuk, Catiana Beatriz; Theill, Laura; Cabeza, Matías Sebastián; et al.; Molecular confirmation of the linkage between the rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistance; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 62; 8; 8-2018; 1-110066-4804CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/lookup/doi/10.1128/AAC.00224-18info:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.00224-18info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T10:52:56Zoai:ri.conicet.gov.ar:11336/89630instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-17 10:52:57.192CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Molecular confirmation of the linkage between the rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistance
title Molecular confirmation of the linkage between the rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistance
spellingShingle Molecular confirmation of the linkage between the rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistance
Macedo, Daiana
AZOLE
CYP51
FLUCONAZOLE
INTRINSIC RESISTANCE
MOLECULAR MECHANISM
MUCORALES
RESISTANCE
RHIZOPUS
VORICONAZOLE
title_short Molecular confirmation of the linkage between the rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistance
title_full Molecular confirmation of the linkage between the rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistance
title_fullStr Molecular confirmation of the linkage between the rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistance
title_full_unstemmed Molecular confirmation of the linkage between the rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistance
title_sort Molecular confirmation of the linkage between the rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistance
dc.creator.none.fl_str_mv Macedo, Daiana
Leonardelli, Florencia
Dudiuk, Catiana Beatriz
Theill, Laura
Cabeza, Matías Sebastián
Gamarra, Soledad
Garcia, Guillermo Manuel
author Macedo, Daiana
author_facet Macedo, Daiana
Leonardelli, Florencia
Dudiuk, Catiana Beatriz
Theill, Laura
Cabeza, Matías Sebastián
Gamarra, Soledad
Garcia, Guillermo Manuel
author_role author
author2 Leonardelli, Florencia
Dudiuk, Catiana Beatriz
Theill, Laura
Cabeza, Matías Sebastián
Gamarra, Soledad
Garcia, Guillermo Manuel
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv AZOLE
CYP51
FLUCONAZOLE
INTRINSIC RESISTANCE
MOLECULAR MECHANISM
MUCORALES
RESISTANCE
RHIZOPUS
VORICONAZOLE
topic AZOLE
CYP51
FLUCONAZOLE
INTRINSIC RESISTANCE
MOLECULAR MECHANISM
MUCORALES
RESISTANCE
RHIZOPUS
VORICONAZOLE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Rhizopus oryzae is the most prevalent causative agent of mucormycosis, an increasingly reported opportunistic fungal infection. These Mucorales are intrinsically resistant to Candida- and Aspergillus-active antifungal azole drugs, such as fluconazole (FLC) and voriconazole, respectively. Despite its importance, the molecular mechanisms of its intrinsic azole resistance have not been elucidated yet. The aim of this work was to establish if the Rhizopus oryzae CYP51 genes are uniquely responsible for intrinsic voriconazole and fluconazole resistance in these fungal pathogens. Two CYP51 genes were identified in the R. oryzae genome. We classified them as CYP51A and CYP51B based on their sequence similarity with other known fungal CYP51 genes. Later, we obtained a chimeric Aspergillus fumigatus strain harboring a functional R. oryzae CYP51A gene expressed under the regulation of the wild-type A. fumigatus CYP51A promoter and terminator. The mutant was selected after transformation by using a novel procedure taking advantage of the FLC hypersusceptibility of the A. fumigatus CYP51A deletion mutant used as the recipient strain. The azole susceptibility patterns of the A. fumigatus transformants harboring R. oryzae CYP51A mimicked exactly the azole susceptibility patterns of this mucormycete. The data presented in this work demonstrate that the R. oryzae CYP51A coding sequence is uniquely responsible for the R. oryzae azole susceptibility patterns.
Fil: Macedo, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Unidad de Administración Territorial; Argentina
Fil: Leonardelli, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Unidad de Administración Territorial; Argentina
Fil: Dudiuk, Catiana Beatriz. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Fil: Theill, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Unidad de Administración Territorial; Argentina
Fil: Cabeza, Matías Sebastián. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Fil: Gamarra, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Unidad de Administración Territorial; Argentina
Fil: Garcia, Guillermo Manuel. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
description Rhizopus oryzae is the most prevalent causative agent of mucormycosis, an increasingly reported opportunistic fungal infection. These Mucorales are intrinsically resistant to Candida- and Aspergillus-active antifungal azole drugs, such as fluconazole (FLC) and voriconazole, respectively. Despite its importance, the molecular mechanisms of its intrinsic azole resistance have not been elucidated yet. The aim of this work was to establish if the Rhizopus oryzae CYP51 genes are uniquely responsible for intrinsic voriconazole and fluconazole resistance in these fungal pathogens. Two CYP51 genes were identified in the R. oryzae genome. We classified them as CYP51A and CYP51B based on their sequence similarity with other known fungal CYP51 genes. Later, we obtained a chimeric Aspergillus fumigatus strain harboring a functional R. oryzae CYP51A gene expressed under the regulation of the wild-type A. fumigatus CYP51A promoter and terminator. The mutant was selected after transformation by using a novel procedure taking advantage of the FLC hypersusceptibility of the A. fumigatus CYP51A deletion mutant used as the recipient strain. The azole susceptibility patterns of the A. fumigatus transformants harboring R. oryzae CYP51A mimicked exactly the azole susceptibility patterns of this mucormycete. The data presented in this work demonstrate that the R. oryzae CYP51A coding sequence is uniquely responsible for the R. oryzae azole susceptibility patterns.
publishDate 2018
dc.date.none.fl_str_mv 2018-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/89630
Macedo, Daiana; Leonardelli, Florencia; Dudiuk, Catiana Beatriz; Theill, Laura; Cabeza, Matías Sebastián; et al.; Molecular confirmation of the linkage between the rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistance; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 62; 8; 8-2018; 1-11
0066-4804
CONICET Digital
CONICET
url http://hdl.handle.net/11336/89630
identifier_str_mv Macedo, Daiana; Leonardelli, Florencia; Dudiuk, Catiana Beatriz; Theill, Laura; Cabeza, Matías Sebastián; et al.; Molecular confirmation of the linkage between the rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistance; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 62; 8; 8-2018; 1-11
0066-4804
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/lookup/doi/10.1128/AAC.00224-18
info:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.00224-18
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.001348

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