Trypanosoma cruzi: Attenuation of virulence and protective immunogenicity after monoallelic disruption of the cub gene

Autores
Barrio, Alejandra; Van Voorhis, Wesley C.; Basombrío, Miguel Ángel Manuel
Año de publicación
2007
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Calmodulin-ubiquitin (cub) is a single-copy gene of Trypanosoma cruzi, which encodes a 208 aminoacid polypeptide of unknown function, containing putative calcium-binding domains. After targeted deletion, a clone (TulCub8) was derived where one of the two alleles was disrupted. This clone displayed a sharp and stable loss of virulence for mice. Parasitemias after inoculation of 106 trypomastigotes of the mutant, as compared to wild-type parasites were 68-fold lower (p = 0.018) in adult Swiss mice and 27-fold lower (p = 0.002) in newborn Balb/c mice. Epimastigote inocula of the mutant were strongly protective against infection by wild-type parasites. Virulence was not restored by serial passage in mice, showing that the attenuated phenotype is stable and gene-conversion from the intact cub allele does not occur at an appreciable rate. Retransfection of the missing cub allele restored virulence. Complementation experiments showed that the intact cub gene is necessary for full expression of virulence.
Fil: Barrio, Alejandra. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina
Fil: Van Voorhis, Wesley C.. University Of Washington Medical Center; Estados Unidos
Fil: Basombrío, Miguel Ángel Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; Argentina
Materia
Attenuation
Calmodulin-Ubiquitin
Calmodulin-Ubiquitin-Associated Gene
Cub
Deoxyribonucleic Acid
Dna
Fbm
Fresh Blood Mount
Lit
Liver Infusion-Tryptose Medium
Pcr
Polymerase-Chain Reaction
Retransfected Line
Rl
T. Cruzi Clone with Monoallelic Deletion Of Cub Gene
Targeted Deletion
Trypanosoma Cruzi
Tulcub8
Virulence
Wild-Type
Wt
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:11336/36597
Acceder
id CONICETDig_b77ad3fc3f7a193fa1c884cdd4bf3555
oai_identifier_str oai:ri.conicet.gov.ar:11336/36597
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Trypanosoma cruzi: Attenuation of virulence and protective immunogenicity after monoallelic disruption of the cub geneBarrio, AlejandraVan Voorhis, Wesley C.Basombrío, Miguel Ángel ManuelAttenuationCalmodulin-UbiquitinCalmodulin-Ubiquitin-Associated GeneCubDeoxyribonucleic AcidDnaFbmFresh Blood MountLitLiver Infusion-Tryptose MediumPcrPolymerase-Chain ReactionRetransfected LineRlT. Cruzi Clone with Monoallelic Deletion Of Cub GeneTargeted DeletionTrypanosoma CruziTulcub8VirulenceWild-TypeWthttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Calmodulin-ubiquitin (cub) is a single-copy gene of Trypanosoma cruzi, which encodes a 208 aminoacid polypeptide of unknown function, containing putative calcium-binding domains. After targeted deletion, a clone (TulCub8) was derived where one of the two alleles was disrupted. This clone displayed a sharp and stable loss of virulence for mice. Parasitemias after inoculation of 106 trypomastigotes of the mutant, as compared to wild-type parasites were 68-fold lower (p = 0.018) in adult Swiss mice and 27-fold lower (p = 0.002) in newborn Balb/c mice. Epimastigote inocula of the mutant were strongly protective against infection by wild-type parasites. Virulence was not restored by serial passage in mice, showing that the attenuated phenotype is stable and gene-conversion from the intact cub allele does not occur at an appreciable rate. Retransfection of the missing cub allele restored virulence. Complementation experiments showed that the intact cub gene is necessary for full expression of virulence.Fil: Barrio, Alejandra. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Van Voorhis, Wesley C.. University Of Washington Medical Center; Estados UnidosFil: Basombrío, Miguel Ángel Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; ArgentinaElsevier2007-12info: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/11336/36597Barrio, Alejandra; Van Voorhis, Wesley C.; Basombrío, Miguel Ángel Manuel; Trypanosoma cruzi: Attenuation of virulence and protective immunogenicity after monoallelic disruption of the cub gene; Elsevier; Experimental Parasitology; 117; 4; 12-2007; 382-3890014-4894CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2007.05.005info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0014489407001397info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:29:22Zoai:ri.conicet.gov.ar:11336/36597instacron: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:34982025-10-22 11:29:23.123CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Trypanosoma cruzi: Attenuation of virulence and protective immunogenicity after monoallelic disruption of the cub gene
title Trypanosoma cruzi: Attenuation of virulence and protective immunogenicity after monoallelic disruption of the cub gene
spellingShingle Trypanosoma cruzi: Attenuation of virulence and protective immunogenicity after monoallelic disruption of the cub gene
Barrio, Alejandra
Attenuation
Calmodulin-Ubiquitin
Calmodulin-Ubiquitin-Associated Gene
Cub
Deoxyribonucleic Acid
Dna
Fbm
Fresh Blood Mount
Lit
Liver Infusion-Tryptose Medium
Pcr
Polymerase-Chain Reaction
Retransfected Line
Rl
T. Cruzi Clone with Monoallelic Deletion Of Cub Gene
Targeted Deletion
Trypanosoma Cruzi
Tulcub8
Virulence
Wild-Type
Wt
title_short Trypanosoma cruzi: Attenuation of virulence and protective immunogenicity after monoallelic disruption of the cub gene
title_full Trypanosoma cruzi: Attenuation of virulence and protective immunogenicity after monoallelic disruption of the cub gene
title_fullStr Trypanosoma cruzi: Attenuation of virulence and protective immunogenicity after monoallelic disruption of the cub gene
title_full_unstemmed Trypanosoma cruzi: Attenuation of virulence and protective immunogenicity after monoallelic disruption of the cub gene
title_sort Trypanosoma cruzi: Attenuation of virulence and protective immunogenicity after monoallelic disruption of the cub gene
dc.creator.none.fl_str_mv Barrio, Alejandra
Van Voorhis, Wesley C.
Basombrío, Miguel Ángel Manuel
author Barrio, Alejandra
author_facet Barrio, Alejandra
Van Voorhis, Wesley C.
Basombrío, Miguel Ángel Manuel
author_role author
author2 Van Voorhis, Wesley C.
Basombrío, Miguel Ángel Manuel
author2_role author
author
dc.subject.none.fl_str_mv Attenuation
Calmodulin-Ubiquitin
Calmodulin-Ubiquitin-Associated Gene
Cub
Deoxyribonucleic Acid
Dna
Fbm
Fresh Blood Mount
Lit
Liver Infusion-Tryptose Medium
Pcr
Polymerase-Chain Reaction
Retransfected Line
Rl
T. Cruzi Clone with Monoallelic Deletion Of Cub Gene
Targeted Deletion
Trypanosoma Cruzi
Tulcub8
Virulence
Wild-Type
Wt
topic Attenuation
Calmodulin-Ubiquitin
Calmodulin-Ubiquitin-Associated Gene
Cub
Deoxyribonucleic Acid
Dna
Fbm
Fresh Blood Mount
Lit
Liver Infusion-Tryptose Medium
Pcr
Polymerase-Chain Reaction
Retransfected Line
Rl
T. Cruzi Clone with Monoallelic Deletion Of Cub Gene
Targeted Deletion
Trypanosoma Cruzi
Tulcub8
Virulence
Wild-Type
Wt
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Calmodulin-ubiquitin (cub) is a single-copy gene of Trypanosoma cruzi, which encodes a 208 aminoacid polypeptide of unknown function, containing putative calcium-binding domains. After targeted deletion, a clone (TulCub8) was derived where one of the two alleles was disrupted. This clone displayed a sharp and stable loss of virulence for mice. Parasitemias after inoculation of 106 trypomastigotes of the mutant, as compared to wild-type parasites were 68-fold lower (p = 0.018) in adult Swiss mice and 27-fold lower (p = 0.002) in newborn Balb/c mice. Epimastigote inocula of the mutant were strongly protective against infection by wild-type parasites. Virulence was not restored by serial passage in mice, showing that the attenuated phenotype is stable and gene-conversion from the intact cub allele does not occur at an appreciable rate. Retransfection of the missing cub allele restored virulence. Complementation experiments showed that the intact cub gene is necessary for full expression of virulence.
Fil: Barrio, Alejandra. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina
Fil: Van Voorhis, Wesley C.. University Of Washington Medical Center; Estados Unidos
Fil: Basombrío, Miguel Ángel Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; Argentina
description Calmodulin-ubiquitin (cub) is a single-copy gene of Trypanosoma cruzi, which encodes a 208 aminoacid polypeptide of unknown function, containing putative calcium-binding domains. After targeted deletion, a clone (TulCub8) was derived where one of the two alleles was disrupted. This clone displayed a sharp and stable loss of virulence for mice. Parasitemias after inoculation of 106 trypomastigotes of the mutant, as compared to wild-type parasites were 68-fold lower (p = 0.018) in adult Swiss mice and 27-fold lower (p = 0.002) in newborn Balb/c mice. Epimastigote inocula of the mutant were strongly protective against infection by wild-type parasites. Virulence was not restored by serial passage in mice, showing that the attenuated phenotype is stable and gene-conversion from the intact cub allele does not occur at an appreciable rate. Retransfection of the missing cub allele restored virulence. Complementation experiments showed that the intact cub gene is necessary for full expression of virulence.
publishDate 2007
dc.date.none.fl_str_mv 2007-12
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/11336/36597
Barrio, Alejandra; Van Voorhis, Wesley C.; Basombrío, Miguel Ángel Manuel; Trypanosoma cruzi: Attenuation of virulence and protective immunogenicity after monoallelic disruption of the cub gene; Elsevier; Experimental Parasitology; 117; 4; 12-2007; 382-389
0014-4894
CONICET Digital
CONICET
url http://hdl.handle.net/11336/36597
identifier_str_mv Barrio, Alejandra; Van Voorhis, Wesley C.; Basombrío, Miguel Ángel Manuel; Trypanosoma cruzi: Attenuation of virulence and protective immunogenicity after monoallelic disruption of the cub gene; Elsevier; Experimental Parasitology; 117; 4; 12-2007; 382-389
0014-4894
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2007.05.005
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0014489407001397
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 Elsevier
publisher.none.fl_str_mv Elsevier
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
_version_ 1846781879511941120
score 12.982451

Publicaciones similares