NcGRA7 and NcROP40 Play a Role in the Virulence of Neospora caninum in a Pregnant Mouse Model

The intraspecific variability among Neospora caninum isolates in their in vitro behaviour and in vivo virulence has been widely studied. In particular, transcriptomic and proteomic analyses have shown a higher expression/abundance of specific genes/proteins in high-virulence isolates. Consequently,...

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Autores: Rico San Román, Laura, Amieva, Rafael, Regidor Cerrillo, Javier, García Sánchez, Marta Eulalia, Collantes Fernández, Esther, Pastor Fernández, Iván, Saeij, Jeroen P. J., Ortega Mora, Luis Miguel, Horcajo Iglesias, María Del Pilar
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/73212
Acceso en línea:https://hdl.handle.net/20.500.14352/73212
Access Level:acceso abierto
Palabra clave:Neospora caninum
NcGRA7 protein
NcROP40 protein
CRISPR/Cas9
BALB/c
Pregnant mouse model
Virulence factor
Patología veterinaria
3109.07 Patología
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oai_identifier_str oai:docta.ucm.es:20.500.14352/73212
network_acronym_str ES
network_name_str España
repository_id_str
spelling NcGRA7 and NcROP40 Play a Role in the Virulence of Neospora caninum in a Pregnant Mouse ModelRico San Román, LauraAmieva, RafaelRegidor Cerrillo, JavierGarcía Sánchez, Marta EulaliaCollantes Fernández, EstherPastor Fernández, IvánSaeij, Jeroen P. J.Ortega Mora, Luis MiguelHorcajo Iglesias, María Del PilarNeospora caninumNcGRA7 proteinNcROP40 proteinCRISPR/Cas9BALB/cPregnant mouse modelVirulence factorPatología veterinaria3109.07 PatologíaThe intraspecific variability among Neospora caninum isolates in their in vitro behaviour and in vivo virulence has been widely studied. In particular, transcriptomic and proteomic analyses have shown a higher expression/abundance of specific genes/proteins in high-virulence isolates. Consequently, the dense granule protein NcGRA7 and the rhoptry protein NcROP40 were proposed as potential virulence factors. The objective of this study was to characterize the role of these proteins using CRISPR/Cas9 knockout (KO) parasites in a well-established pregnant BALB/c mouse model of N. caninum infection at midgestation. The deletion of NcGRA7 and NcROP40 was associated with a reduction of virulence, as infected dams displayed milder clinical signs, lower parasite burdens in the brain, and reduced mortality rates compared to those infected with the wild-type parasite (Nc-Spain7). Specifically, those infected with the NcGRA7 KO parasites displayed significantly milder clinical signs and a lower brain parasite burden. The median survival time of the pups from dams infected with the two KO parasites was significantly increased, but differences in neonatal mortality rates were not detected. Overall, the present study indicates that the disruption of NcGRA7 considerably impairs virulence in mice, while the impact of NcROP40 deletion was more modest. Further research is needed to understand the role of these virulence factors during N. caninum infection.MPDIUniversidad Complutense de Madrid20222022-08-3120222022-08-31journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/73212reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/732122026-06-02T12:44:21Z
dc.title.none.fl_str_mv NcGRA7 and NcROP40 Play a Role in the Virulence of Neospora caninum in a Pregnant Mouse Model
title NcGRA7 and NcROP40 Play a Role in the Virulence of Neospora caninum in a Pregnant Mouse Model
spellingShingle NcGRA7 and NcROP40 Play a Role in the Virulence of Neospora caninum in a Pregnant Mouse Model
Rico San Román, Laura
Neospora caninum
NcGRA7 protein
NcROP40 protein
CRISPR/Cas9
BALB/c
Pregnant mouse model
Virulence factor
Patología veterinaria
3109.07 Patología
title_short NcGRA7 and NcROP40 Play a Role in the Virulence of Neospora caninum in a Pregnant Mouse Model
title_full NcGRA7 and NcROP40 Play a Role in the Virulence of Neospora caninum in a Pregnant Mouse Model
title_fullStr NcGRA7 and NcROP40 Play a Role in the Virulence of Neospora caninum in a Pregnant Mouse Model
title_full_unstemmed NcGRA7 and NcROP40 Play a Role in the Virulence of Neospora caninum in a Pregnant Mouse Model
title_sort NcGRA7 and NcROP40 Play a Role in the Virulence of Neospora caninum in a Pregnant Mouse Model
dc.creator.none.fl_str_mv Rico San Román, Laura
Amieva, Rafael
Regidor Cerrillo, Javier
García Sánchez, Marta Eulalia
Collantes Fernández, Esther
Pastor Fernández, Iván
Saeij, Jeroen P. J.
Ortega Mora, Luis Miguel
Horcajo Iglesias, María Del Pilar
author Rico San Román, Laura
author_facet Rico San Román, Laura
Amieva, Rafael
Regidor Cerrillo, Javier
García Sánchez, Marta Eulalia
Collantes Fernández, Esther
Pastor Fernández, Iván
Saeij, Jeroen P. J.
Ortega Mora, Luis Miguel
Horcajo Iglesias, María Del Pilar
author_role author
author2 Amieva, Rafael
Regidor Cerrillo, Javier
García Sánchez, Marta Eulalia
Collantes Fernández, Esther
Pastor Fernández, Iván
Saeij, Jeroen P. J.
Ortega Mora, Luis Miguel
Horcajo Iglesias, María Del Pilar
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv Neospora caninum
NcGRA7 protein
NcROP40 protein
CRISPR/Cas9
BALB/c
Pregnant mouse model
Virulence factor
Patología veterinaria
3109.07 Patología
topic Neospora caninum
NcGRA7 protein
NcROP40 protein
CRISPR/Cas9
BALB/c
Pregnant mouse model
Virulence factor
Patología veterinaria
3109.07 Patología
description The intraspecific variability among Neospora caninum isolates in their in vitro behaviour and in vivo virulence has been widely studied. In particular, transcriptomic and proteomic analyses have shown a higher expression/abundance of specific genes/proteins in high-virulence isolates. Consequently, the dense granule protein NcGRA7 and the rhoptry protein NcROP40 were proposed as potential virulence factors. The objective of this study was to characterize the role of these proteins using CRISPR/Cas9 knockout (KO) parasites in a well-established pregnant BALB/c mouse model of N. caninum infection at midgestation. The deletion of NcGRA7 and NcROP40 was associated with a reduction of virulence, as infected dams displayed milder clinical signs, lower parasite burdens in the brain, and reduced mortality rates compared to those infected with the wild-type parasite (Nc-Spain7). Specifically, those infected with the NcGRA7 KO parasites displayed significantly milder clinical signs and a lower brain parasite burden. The median survival time of the pups from dams infected with the two KO parasites was significantly increased, but differences in neonatal mortality rates were not detected. Overall, the present study indicates that the disruption of NcGRA7 considerably impairs virulence in mice, while the impact of NcROP40 deletion was more modest. Further research is needed to understand the role of these virulence factors during N. caninum infection.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-08-31
2022
2022-08-31
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/73212
url https://hdl.handle.net/20.500.14352/73212
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MPDI
publisher.none.fl_str_mv MPDI
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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