Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance

Autores
Ben Ami, Ronen; Garcia, Guillermo Manuel; Lewis, Rusell E.; Gamarra, Maria Soledad; Leventakos, Konstantinos; Perlin, David S.; Kontoyiannis, Dimitrios P.
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The identification of FKS1 mutations in Candida albicans associated with echinocandin resistance has raised concerns over the spread of drug-resistant strains. We studied the impact of fks1 mutations on C. albicans virulence and fitness. Compared with wild-type strains for FKS1, echinocandin-resistant C. albicans strains with homozygous fks1 hot-spot mutations had reduced maximum catalytic capacity of their glucan synthase complexes and thicker cell walls attributable to increased cell wall chitin content. The fks1 mutants with the highest chitin contents had reduced growth rates and impaired filamentation capacities. Fks1 mutants were hypovirulent in fly and mouse models of candidiasis, and this phenotype correlated with the cell wall chitin content. In addition, we observed reduced fitness of echinocandin-resistant C. albicans in competitive mixed infection models. We conclude that fks1 mutations that confer echinocandin resistance come at fitness and virulence costs, which may limit their epidemiological and clinical impact.
Fil: Ben Ami, Ronen. University of Texas; Estados Unidos
Fil: Garcia, Guillermo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Public Health Research Institute; Estados Unidos. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Fil: Lewis, Rusell E.. University of Texas; Estados Unidos. University Of Houston; Estados Unidos
Fil: Gamarra, Maria Soledad. Public Health Research Institute; Estados Unidos
Fil: Leventakos, Konstantinos. University of Texas; Estados Unidos
Fil: Perlin, David S.. Public Health Research Institute; Estados Unidos
Fil: Kontoyiannis, Dimitrios P.. University of Texas; Estados Unidos. University Of Houston; Estados Unidos
Materia
Fks1
Echinocandin
Resistant
Virulence
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:11336/73993
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/73993
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistanceBen Ami, RonenGarcia, Guillermo ManuelLewis, Rusell E.Gamarra, Maria SoledadLeventakos, KonstantinosPerlin, David S.Kontoyiannis, Dimitrios P.Fks1EchinocandinResistantVirulencehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The identification of FKS1 mutations in Candida albicans associated with echinocandin resistance has raised concerns over the spread of drug-resistant strains. We studied the impact of fks1 mutations on C. albicans virulence and fitness. Compared with wild-type strains for FKS1, echinocandin-resistant C. albicans strains with homozygous fks1 hot-spot mutations had reduced maximum catalytic capacity of their glucan synthase complexes and thicker cell walls attributable to increased cell wall chitin content. The fks1 mutants with the highest chitin contents had reduced growth rates and impaired filamentation capacities. Fks1 mutants were hypovirulent in fly and mouse models of candidiasis, and this phenotype correlated with the cell wall chitin content. In addition, we observed reduced fitness of echinocandin-resistant C. albicans in competitive mixed infection models. We conclude that fks1 mutations that confer echinocandin resistance come at fitness and virulence costs, which may limit their epidemiological and clinical impact.Fil: Ben Ami, Ronen. University of Texas; Estados UnidosFil: Garcia, Guillermo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Public Health Research Institute; Estados Unidos. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Lewis, Rusell E.. University of Texas; Estados Unidos. University Of Houston; Estados UnidosFil: Gamarra, Maria Soledad. Public Health Research Institute; Estados UnidosFil: Leventakos, Konstantinos. University of Texas; Estados UnidosFil: Perlin, David S.. Public Health Research Institute; Estados UnidosFil: Kontoyiannis, Dimitrios P.. University of Texas; Estados Unidos. University Of Houston; Estados UnidosUniversity of Chicago Press2011-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/73993Ben Ami, Ronen; Garcia, Guillermo Manuel; Lewis, Rusell E.; Gamarra, Maria Soledad; Leventakos, Konstantinos; et al.; Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance; University of Chicago Press; Journal Of Infectious Diseases; 204; 4; 8-2011; 626-6350022-1899CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1093/infdis/jir351info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jid/article/204/4/626/2192577info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-12T09:34:32Zoai:ri.conicet.gov.ar:11336/73993instacron: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:34982025-11-12 09:34:32.991CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance
title Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance
spellingShingle Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance
Ben Ami, Ronen
Fks1
Echinocandin
Resistant
Virulence
title_short Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance
title_full Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance
title_fullStr Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance
title_full_unstemmed Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance
title_sort Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance
dc.creator.none.fl_str_mv Ben Ami, Ronen
Garcia, Guillermo Manuel
Lewis, Rusell E.
Gamarra, Maria Soledad
Leventakos, Konstantinos
Perlin, David S.
Kontoyiannis, Dimitrios P.
author Ben Ami, Ronen
author_facet Ben Ami, Ronen
Garcia, Guillermo Manuel
Lewis, Rusell E.
Gamarra, Maria Soledad
Leventakos, Konstantinos
Perlin, David S.
Kontoyiannis, Dimitrios P.
author_role author
author2 Garcia, Guillermo Manuel
Lewis, Rusell E.
Gamarra, Maria Soledad
Leventakos, Konstantinos
Perlin, David S.
Kontoyiannis, Dimitrios P.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Fks1
Echinocandin
Resistant
Virulence
topic Fks1
Echinocandin
Resistant
Virulence
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The identification of FKS1 mutations in Candida albicans associated with echinocandin resistance has raised concerns over the spread of drug-resistant strains. We studied the impact of fks1 mutations on C. albicans virulence and fitness. Compared with wild-type strains for FKS1, echinocandin-resistant C. albicans strains with homozygous fks1 hot-spot mutations had reduced maximum catalytic capacity of their glucan synthase complexes and thicker cell walls attributable to increased cell wall chitin content. The fks1 mutants with the highest chitin contents had reduced growth rates and impaired filamentation capacities. Fks1 mutants were hypovirulent in fly and mouse models of candidiasis, and this phenotype correlated with the cell wall chitin content. In addition, we observed reduced fitness of echinocandin-resistant C. albicans in competitive mixed infection models. We conclude that fks1 mutations that confer echinocandin resistance come at fitness and virulence costs, which may limit their epidemiological and clinical impact.
Fil: Ben Ami, Ronen. University of Texas; Estados Unidos
Fil: Garcia, Guillermo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Public Health Research Institute; Estados Unidos. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Fil: Lewis, Rusell E.. University of Texas; Estados Unidos. University Of Houston; Estados Unidos
Fil: Gamarra, Maria Soledad. Public Health Research Institute; Estados Unidos
Fil: Leventakos, Konstantinos. University of Texas; Estados Unidos
Fil: Perlin, David S.. Public Health Research Institute; Estados Unidos
Fil: Kontoyiannis, Dimitrios P.. University of Texas; Estados Unidos. University Of Houston; Estados Unidos
description The identification of FKS1 mutations in Candida albicans associated with echinocandin resistance has raised concerns over the spread of drug-resistant strains. We studied the impact of fks1 mutations on C. albicans virulence and fitness. Compared with wild-type strains for FKS1, echinocandin-resistant C. albicans strains with homozygous fks1 hot-spot mutations had reduced maximum catalytic capacity of their glucan synthase complexes and thicker cell walls attributable to increased cell wall chitin content. The fks1 mutants with the highest chitin contents had reduced growth rates and impaired filamentation capacities. Fks1 mutants were hypovirulent in fly and mouse models of candidiasis, and this phenotype correlated with the cell wall chitin content. In addition, we observed reduced fitness of echinocandin-resistant C. albicans in competitive mixed infection models. We conclude that fks1 mutations that confer echinocandin resistance come at fitness and virulence costs, which may limit their epidemiological and clinical impact.
publishDate 2011
dc.date.none.fl_str_mv 2011-08
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/11336/73993
Ben Ami, Ronen; Garcia, Guillermo Manuel; Lewis, Rusell E.; Gamarra, Maria Soledad; Leventakos, Konstantinos; et al.; Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance; University of Chicago Press; Journal Of Infectious Diseases; 204; 4; 8-2011; 626-635
0022-1899
CONICET Digital
CONICET
url http://hdl.handle.net/11336/73993
identifier_str_mv Ben Ami, Ronen; Garcia, Guillermo Manuel; Lewis, Rusell E.; Gamarra, Maria Soledad; Leventakos, Konstantinos; et al.; Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance; University of Chicago Press; Journal Of Infectious Diseases; 204; 4; 8-2011; 626-635
0022-1899
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1093/infdis/jir351
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jid/article/204/4/626/2192577
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
dc.publisher.none.fl_str_mv University of Chicago Press
publisher.none.fl_str_mv University of Chicago Press
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 13.24909

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