Attenuation of a local Mycobacterium avium subsp paratuberculosis virulent strain by homologous recombination

Autores
Colombatti Olivieri, Maria Alejandra; Moyano, Roberto Damian; Nagel, Ariel Gaston; Gravisaco, María José; Delgado, Fernando Oscar; Alvarado Pinedo, Maria Fiorella; Travería, Gabriel Eduardo; Alonso, Maria Natalia
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Paratuberculosis (PTB) is a disease that affects many countries around the world. One of the strategies that could contribute to its control is the development of effective vaccines that prevent the dissemination of Mycobacterium avium subsp. paratuberculosis, the causal agent. Previously, we showed the humoral and cellular immune response induced by a novel vaccine candidate against PTB based on the inactivated Map6611 virulent strain. In the present study, we independently deleted two operons, mce4 and lprG-p55, possibly associated with Map virulence. Map6611_Δmce4 and Map6611_ΔlprG-p55 virulence and immune response were evaluated in two experimental models. We observed that the deletion of mce4 does not attenuate Map6611 virulence in bovine macrophages or mice but induced significant lesions in mice and increased proinflammatory cytokines production. On the other hand, we observed that the deletion of lprG-p55 attenuates the virulence of Map6611 in both experimental models and induces a significant immune response. The results of this work demonstrated the role of both operons in Map pathogenesis and suggested that the attenuated mutant Map6611_ΔlprG-p55 could be evaluated in the future as a live vaccine candidate.
Instituto de Biotecnología
Fil: Colombatti Olivieri, Maria Alejandra. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Colombatti Olivieri, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Moyano, Roberto Damian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Moyano, Roberto Damian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Nagel, Ariel Gaston. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Nagel, Ariel Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gravisaco, María José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Gravisaco, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Delgado, Fernando Oscar. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina
Fil: Alvarado Pinedo, María Fiorella. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Centro de Diagnóstico e Investigaciones Veterinarias; Argentina
Fil: Travería, Gabriel Eduardo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Centro de Diagnóstico e Investigaciones Veterinarias; Argentina
Fil: Alonso Maria Natalia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Alonso Maria Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fuente
Research in Veterinary Science 193 : 105758. (September 2025)
Materia
Mycobacterium avium subsp. paratuberculosis
Immune Response
Vaccines
Vaccination
Virulence
Respuesta Inmunológica
Vacuna
Vacunación
Virulencia
Nivel de accesibilidad
acceso restringido
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/25360
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oai_identifier_str oai:localhost:20.500.12123/25360
network_acronym_str INTADig
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network_name_str INTA Digital (INTA)
spelling Attenuation of a local Mycobacterium avium subsp paratuberculosis virulent strain by homologous recombinationColombatti Olivieri, Maria AlejandraMoyano, Roberto DamianNagel, Ariel GastonGravisaco, María JoséDelgado, Fernando OscarAlvarado Pinedo, Maria FiorellaTravería, Gabriel EduardoAlonso, Maria NataliaMycobacterium avium subsp. paratuberculosisImmune ResponseVaccinesVaccinationVirulenceRespuesta InmunológicaVacunaVacunaciónVirulenciaParatuberculosis (PTB) is a disease that affects many countries around the world. One of the strategies that could contribute to its control is the development of effective vaccines that prevent the dissemination of Mycobacterium avium subsp. paratuberculosis, the causal agent. Previously, we showed the humoral and cellular immune response induced by a novel vaccine candidate against PTB based on the inactivated Map6611 virulent strain. In the present study, we independently deleted two operons, mce4 and lprG-p55, possibly associated with Map virulence. Map6611_Δmce4 and Map6611_ΔlprG-p55 virulence and immune response were evaluated in two experimental models. We observed that the deletion of mce4 does not attenuate Map6611 virulence in bovine macrophages or mice but induced significant lesions in mice and increased proinflammatory cytokines production. On the other hand, we observed that the deletion of lprG-p55 attenuates the virulence of Map6611 in both experimental models and induces a significant immune response. The results of this work demonstrated the role of both operons in Map pathogenesis and suggested that the attenuated mutant Map6611_ΔlprG-p55 could be evaluated in the future as a live vaccine candidate.Instituto de BiotecnologíaFil: Colombatti Olivieri, Maria Alejandra. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Colombatti Olivieri, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Moyano, Roberto Damian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Moyano, Roberto Damian. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nagel, Ariel Gaston. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Nagel, Ariel Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gravisaco, María José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Gravisaco, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Delgado, Fernando Oscar. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Alvarado Pinedo, María Fiorella. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Centro de Diagnóstico e Investigaciones Veterinarias; ArgentinaFil: Travería, Gabriel Eduardo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Centro de Diagnóstico e Investigaciones Veterinarias; ArgentinaFil: Alonso Maria Natalia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Alonso Maria Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier2026-03-05T12:19:04Z2026-03-05T12:19:04Z2025-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/25360https://www.sciencedirect.com/science/article/abs/pii/S00345288250023220034-52881532-2661https://doi.org/10.1016/j.rvsc.2025.105758Research in Veterinary Science 193 : 105758. (September 2025)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/restrictedAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2026-03-26T11:25:29Zoai:localhost:20.500.12123/25360instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2026-03-26 11:25:30.218INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Attenuation of a local Mycobacterium avium subsp paratuberculosis virulent strain by homologous recombination
title Attenuation of a local Mycobacterium avium subsp paratuberculosis virulent strain by homologous recombination
spellingShingle Attenuation of a local Mycobacterium avium subsp paratuberculosis virulent strain by homologous recombination
Colombatti Olivieri, Maria Alejandra
Mycobacterium avium subsp. paratuberculosis
Immune Response
Vaccines
Vaccination
Virulence
Respuesta Inmunológica
Vacuna
Vacunación
Virulencia
title_short Attenuation of a local Mycobacterium avium subsp paratuberculosis virulent strain by homologous recombination
title_full Attenuation of a local Mycobacterium avium subsp paratuberculosis virulent strain by homologous recombination
title_fullStr Attenuation of a local Mycobacterium avium subsp paratuberculosis virulent strain by homologous recombination
title_full_unstemmed Attenuation of a local Mycobacterium avium subsp paratuberculosis virulent strain by homologous recombination
title_sort Attenuation of a local Mycobacterium avium subsp paratuberculosis virulent strain by homologous recombination
dc.creator.none.fl_str_mv Colombatti Olivieri, Maria Alejandra
Moyano, Roberto Damian
Nagel, Ariel Gaston
Gravisaco, María José
Delgado, Fernando Oscar
Alvarado Pinedo, Maria Fiorella
Travería, Gabriel Eduardo
Alonso, Maria Natalia
author Colombatti Olivieri, Maria Alejandra
author_facet Colombatti Olivieri, Maria Alejandra
Moyano, Roberto Damian
Nagel, Ariel Gaston
Gravisaco, María José
Delgado, Fernando Oscar
Alvarado Pinedo, Maria Fiorella
Travería, Gabriel Eduardo
Alonso, Maria Natalia
author_role author
author2 Moyano, Roberto Damian
Nagel, Ariel Gaston
Gravisaco, María José
Delgado, Fernando Oscar
Alvarado Pinedo, Maria Fiorella
Travería, Gabriel Eduardo
Alonso, Maria Natalia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mycobacterium avium subsp. paratuberculosis
Immune Response
Vaccines
Vaccination
Virulence
Respuesta Inmunológica
Vacuna
Vacunación
Virulencia
topic Mycobacterium avium subsp. paratuberculosis
Immune Response
Vaccines
Vaccination
Virulence
Respuesta Inmunológica
Vacuna
Vacunación
Virulencia
dc.description.none.fl_txt_mv Paratuberculosis (PTB) is a disease that affects many countries around the world. One of the strategies that could contribute to its control is the development of effective vaccines that prevent the dissemination of Mycobacterium avium subsp. paratuberculosis, the causal agent. Previously, we showed the humoral and cellular immune response induced by a novel vaccine candidate against PTB based on the inactivated Map6611 virulent strain. In the present study, we independently deleted two operons, mce4 and lprG-p55, possibly associated with Map virulence. Map6611_Δmce4 and Map6611_ΔlprG-p55 virulence and immune response were evaluated in two experimental models. We observed that the deletion of mce4 does not attenuate Map6611 virulence in bovine macrophages or mice but induced significant lesions in mice and increased proinflammatory cytokines production. On the other hand, we observed that the deletion of lprG-p55 attenuates the virulence of Map6611 in both experimental models and induces a significant immune response. The results of this work demonstrated the role of both operons in Map pathogenesis and suggested that the attenuated mutant Map6611_ΔlprG-p55 could be evaluated in the future as a live vaccine candidate.
Instituto de Biotecnología
Fil: Colombatti Olivieri, Maria Alejandra. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Colombatti Olivieri, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Moyano, Roberto Damian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Moyano, Roberto Damian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Nagel, Ariel Gaston. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Nagel, Ariel Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gravisaco, María José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Gravisaco, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Delgado, Fernando Oscar. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina
Fil: Alvarado Pinedo, María Fiorella. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Centro de Diagnóstico e Investigaciones Veterinarias; Argentina
Fil: Travería, Gabriel Eduardo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Centro de Diagnóstico e Investigaciones Veterinarias; Argentina
Fil: Alonso Maria Natalia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Alonso Maria Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Paratuberculosis (PTB) is a disease that affects many countries around the world. One of the strategies that could contribute to its control is the development of effective vaccines that prevent the dissemination of Mycobacterium avium subsp. paratuberculosis, the causal agent. Previously, we showed the humoral and cellular immune response induced by a novel vaccine candidate against PTB based on the inactivated Map6611 virulent strain. In the present study, we independently deleted two operons, mce4 and lprG-p55, possibly associated with Map virulence. Map6611_Δmce4 and Map6611_ΔlprG-p55 virulence and immune response were evaluated in two experimental models. We observed that the deletion of mce4 does not attenuate Map6611 virulence in bovine macrophages or mice but induced significant lesions in mice and increased proinflammatory cytokines production. On the other hand, we observed that the deletion of lprG-p55 attenuates the virulence of Map6611 in both experimental models and induces a significant immune response. The results of this work demonstrated the role of both operons in Map pathogenesis and suggested that the attenuated mutant Map6611_ΔlprG-p55 could be evaluated in the future as a live vaccine candidate.
publishDate 2025
dc.date.none.fl_str_mv 2025-09
2026-03-05T12:19:04Z
2026-03-05T12:19:04Z
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/20.500.12123/25360
https://www.sciencedirect.com/science/article/abs/pii/S0034528825002322
0034-5288
1532-2661
https://doi.org/10.1016/j.rvsc.2025.105758
url http://hdl.handle.net/20.500.12123/25360
https://www.sciencedirect.com/science/article/abs/pii/S0034528825002322
https://doi.org/10.1016/j.rvsc.2025.105758
identifier_str_mv 0034-5288
1532-2661
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv restrictedAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Research in Veterinary Science 193 : 105758. (September 2025)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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