Performance of the PhoP (Rv0757/Mb0780) protein as diagnostic antigen for bovine tuberculosis

Autores
Ferrara Muñiz, Ximena; Marques Da Silva, Wanderson; Garbaccio, Sergio Gabriel; Garro, Carlos Javier; Sammarruco, Romina Ayelén; Encinas, Micaela; Carignano, Hugo Adrian; Bianco, María Veronica; Zumarraga, Martin Jose; Cataldi, Angel Adrian; Eirin, Maria Emilia
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Bovine tuberculosis (bTB), a global zoonotic disease, causes negative effects on human and animal health. PhoP protein is a key regulator of pathogenic phenotypes in members of the Mycobacterium tuberculosis complex, which includes the causative agent of bTB. Despite extensive research on this protein focused in deciphering its regulatory role, little was explored about it as a diagnostic antigen. In humans, a novel role of anti-PhoP antibodies as a possible marker for the diagnosis of TB was demonstrated. However, this issue was not addressed in bovines. In this study, antigenic properties of the PhoP protein were evaluated in naturally Mycobacterium bovis (M. bovis) infected bovines. A high homology of PhoP (≥ 75 %) was observed in environmental mycobacterial species and other genera such as Salmonella and Pasteurella. Using the IFN-gamma release assay (IGRA), we detected cell-mediated immune response against PhoP in cattle from infected herds (25 %; IC 95 % 3.2–65.1), although it was significantly lower than that evoked by the reference antigens, ESAT-6/CFP-10/Rv3615c (75 %; IC95 % 34.9–96.8), and the purified protein derivative (87.5 %; IC 95 % 47.4–99.7) (p < 0.05)). Animals from a bTB free area showed no response against PhoP when analyzed by IGRA. Although, the humoral response detected 62.5 % (CI95% 24.5–91.5) of naturally infected animals, there was 100 % cross-reactivity among TB-free cattle. These results suggest that the PhoP protein is not a promising candidate for bTB diagnosis, due to it had relatively low levels of test sensitivity in the IGRA test, and very low specificity in a humoral antibody western blot assay.
Instituto de Biotecnología
Fil: Ferrara Muñiz, Ximena. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Ferrara Muñiz, Ximena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Marques Da Silva, Wanderson. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Marques Da Silva, Wanderson. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garbaccio, Sergio Gabriel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Garbaccio, Sergio Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garro, Carlos Javier. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Garro, Carlos Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sammarruco, Romina Ayelén. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Sammarruco, Romina Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Encinas, Micaela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Encinas, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Carignano, Hugo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Carignano, Hugo Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Bianco, María Veronica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Bianco, María Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Zumarraga, Martin Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Zumarraga, Martin Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cataldi, Angel Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Cataldi, Angel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Eirin, Maria Emilia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Eirin, Maria Emilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fuente
Research in Veterinary Science 184 : 105513 (March 2025)
Materia
Bovine Tuberculosis
Immune Response
Diagnostic Techniques
Antigens
Tuberculosis Bovina
Respuesta Inmunológica
Técnica de Diagnóstico
Antígenos
Mycobacterium bovis
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:20.500.12123/21501
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spelling Performance of the PhoP (Rv0757/Mb0780) protein as diagnostic antigen for bovine tuberculosisFerrara Muñiz, XimenaMarques Da Silva, WandersonGarbaccio, Sergio GabrielGarro, Carlos JavierSammarruco, Romina AyelénEncinas, MicaelaCarignano, Hugo AdrianBianco, María VeronicaZumarraga, Martin JoseCataldi, Angel AdrianEirin, Maria EmiliaBovine TuberculosisImmune ResponseDiagnostic TechniquesAntigensTuberculosis BovinaRespuesta InmunológicaTécnica de DiagnósticoAntígenosMycobacterium bovisBovine tuberculosis (bTB), a global zoonotic disease, causes negative effects on human and animal health. PhoP protein is a key regulator of pathogenic phenotypes in members of the Mycobacterium tuberculosis complex, which includes the causative agent of bTB. Despite extensive research on this protein focused in deciphering its regulatory role, little was explored about it as a diagnostic antigen. In humans, a novel role of anti-PhoP antibodies as a possible marker for the diagnosis of TB was demonstrated. However, this issue was not addressed in bovines. In this study, antigenic properties of the PhoP protein were evaluated in naturally Mycobacterium bovis (M. bovis) infected bovines. A high homology of PhoP (≥ 75 %) was observed in environmental mycobacterial species and other genera such as Salmonella and Pasteurella. Using the IFN-gamma release assay (IGRA), we detected cell-mediated immune response against PhoP in cattle from infected herds (25 %; IC 95 % 3.2–65.1), although it was significantly lower than that evoked by the reference antigens, ESAT-6/CFP-10/Rv3615c (75 %; IC95 % 34.9–96.8), and the purified protein derivative (87.5 %; IC 95 % 47.4–99.7) (p < 0.05)). Animals from a bTB free area showed no response against PhoP when analyzed by IGRA. Although, the humoral response detected 62.5 % (CI95% 24.5–91.5) of naturally infected animals, there was 100 % cross-reactivity among TB-free cattle. These results suggest that the PhoP protein is not a promising candidate for bTB diagnosis, due to it had relatively low levels of test sensitivity in the IGRA test, and very low specificity in a humoral antibody western blot assay.Instituto de BiotecnologíaFil: Ferrara Muñiz, Ximena. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Ferrara Muñiz, Ximena. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marques Da Silva, Wanderson. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Marques Da Silva, Wanderson. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garbaccio, Sergio Gabriel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; ArgentinaFil: Garbaccio, Sergio Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garro, Carlos Javier. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; ArgentinaFil: Garro, Carlos Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sammarruco, Romina Ayelén. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; ArgentinaFil: Sammarruco, Romina Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Encinas, Micaela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Encinas, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carignano, Hugo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carignano, Hugo Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Bianco, María Veronica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Bianco, María Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zumarraga, Martin Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Zumarraga, Martin Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cataldi, Angel Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Cataldi, Angel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Eirin, Maria Emilia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Eirin, Maria Emilia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier2025-02-28T10:36:31Z2025-02-28T10:36:31Z2025-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/21501https://www.sciencedirect.com/science/article/abs/pii/S00345288240038011532-2661https://doi.org/10.1016/j.rvsc.2024.105513Research in Veterinary Science 184 : 105513 (March 2025)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repograntAgreement/INTA/2023-PD-L06-I114, Desarrollo y aplicación de métodos diagnósticos y epidemiológicos para la producción pecuaria sustentable y agroalimentaria en humanos con foco en Una Saludinfo: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)2025-09-29T13:47:10Zoai:localhost:20.500.12123/21501instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-29 13:47:10.547INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Performance of the PhoP (Rv0757/Mb0780) protein as diagnostic antigen for bovine tuberculosis
title Performance of the PhoP (Rv0757/Mb0780) protein as diagnostic antigen for bovine tuberculosis
spellingShingle Performance of the PhoP (Rv0757/Mb0780) protein as diagnostic antigen for bovine tuberculosis
Ferrara Muñiz, Ximena
Bovine Tuberculosis
Immune Response
Diagnostic Techniques
Antigens
Tuberculosis Bovina
Respuesta Inmunológica
Técnica de Diagnóstico
Antígenos
Mycobacterium bovis
title_short Performance of the PhoP (Rv0757/Mb0780) protein as diagnostic antigen for bovine tuberculosis
title_full Performance of the PhoP (Rv0757/Mb0780) protein as diagnostic antigen for bovine tuberculosis
title_fullStr Performance of the PhoP (Rv0757/Mb0780) protein as diagnostic antigen for bovine tuberculosis
title_full_unstemmed Performance of the PhoP (Rv0757/Mb0780) protein as diagnostic antigen for bovine tuberculosis
title_sort Performance of the PhoP (Rv0757/Mb0780) protein as diagnostic antigen for bovine tuberculosis
dc.creator.none.fl_str_mv Ferrara Muñiz, Ximena
Marques Da Silva, Wanderson
Garbaccio, Sergio Gabriel
Garro, Carlos Javier
Sammarruco, Romina Ayelén
Encinas, Micaela
Carignano, Hugo Adrian
Bianco, María Veronica
Zumarraga, Martin Jose
Cataldi, Angel Adrian
Eirin, Maria Emilia
author Ferrara Muñiz, Ximena
author_facet Ferrara Muñiz, Ximena
Marques Da Silva, Wanderson
Garbaccio, Sergio Gabriel
Garro, Carlos Javier
Sammarruco, Romina Ayelén
Encinas, Micaela
Carignano, Hugo Adrian
Bianco, María Veronica
Zumarraga, Martin Jose
Cataldi, Angel Adrian
Eirin, Maria Emilia
author_role author
author2 Marques Da Silva, Wanderson
Garbaccio, Sergio Gabriel
Garro, Carlos Javier
Sammarruco, Romina Ayelén
Encinas, Micaela
Carignano, Hugo Adrian
Bianco, María Veronica
Zumarraga, Martin Jose
Cataldi, Angel Adrian
Eirin, Maria Emilia
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Bovine Tuberculosis
Immune Response
Diagnostic Techniques
Antigens
Tuberculosis Bovina
Respuesta Inmunológica
Técnica de Diagnóstico
Antígenos
Mycobacterium bovis
topic Bovine Tuberculosis
Immune Response
Diagnostic Techniques
Antigens
Tuberculosis Bovina
Respuesta Inmunológica
Técnica de Diagnóstico
Antígenos
Mycobacterium bovis
dc.description.none.fl_txt_mv Bovine tuberculosis (bTB), a global zoonotic disease, causes negative effects on human and animal health. PhoP protein is a key regulator of pathogenic phenotypes in members of the Mycobacterium tuberculosis complex, which includes the causative agent of bTB. Despite extensive research on this protein focused in deciphering its regulatory role, little was explored about it as a diagnostic antigen. In humans, a novel role of anti-PhoP antibodies as a possible marker for the diagnosis of TB was demonstrated. However, this issue was not addressed in bovines. In this study, antigenic properties of the PhoP protein were evaluated in naturally Mycobacterium bovis (M. bovis) infected bovines. A high homology of PhoP (≥ 75 %) was observed in environmental mycobacterial species and other genera such as Salmonella and Pasteurella. Using the IFN-gamma release assay (IGRA), we detected cell-mediated immune response against PhoP in cattle from infected herds (25 %; IC 95 % 3.2–65.1), although it was significantly lower than that evoked by the reference antigens, ESAT-6/CFP-10/Rv3615c (75 %; IC95 % 34.9–96.8), and the purified protein derivative (87.5 %; IC 95 % 47.4–99.7) (p < 0.05)). Animals from a bTB free area showed no response against PhoP when analyzed by IGRA. Although, the humoral response detected 62.5 % (CI95% 24.5–91.5) of naturally infected animals, there was 100 % cross-reactivity among TB-free cattle. These results suggest that the PhoP protein is not a promising candidate for bTB diagnosis, due to it had relatively low levels of test sensitivity in the IGRA test, and very low specificity in a humoral antibody western blot assay.
Instituto de Biotecnología
Fil: Ferrara Muñiz, Ximena. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Ferrara Muñiz, Ximena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Marques Da Silva, Wanderson. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Marques Da Silva, Wanderson. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garbaccio, Sergio Gabriel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Garbaccio, Sergio Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garro, Carlos Javier. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Garro, Carlos Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sammarruco, Romina Ayelén. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología Veterinaria; Argentina
Fil: Sammarruco, Romina Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Encinas, Micaela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Encinas, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Carignano, Hugo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Carignano, Hugo Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Bianco, María Veronica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Bianco, María Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Zumarraga, Martin Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Zumarraga, Martin Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cataldi, Angel Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Cataldi, Angel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Eirin, Maria Emilia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Eirin, Maria Emilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Bovine tuberculosis (bTB), a global zoonotic disease, causes negative effects on human and animal health. PhoP protein is a key regulator of pathogenic phenotypes in members of the Mycobacterium tuberculosis complex, which includes the causative agent of bTB. Despite extensive research on this protein focused in deciphering its regulatory role, little was explored about it as a diagnostic antigen. In humans, a novel role of anti-PhoP antibodies as a possible marker for the diagnosis of TB was demonstrated. However, this issue was not addressed in bovines. In this study, antigenic properties of the PhoP protein were evaluated in naturally Mycobacterium bovis (M. bovis) infected bovines. A high homology of PhoP (≥ 75 %) was observed in environmental mycobacterial species and other genera such as Salmonella and Pasteurella. Using the IFN-gamma release assay (IGRA), we detected cell-mediated immune response against PhoP in cattle from infected herds (25 %; IC 95 % 3.2–65.1), although it was significantly lower than that evoked by the reference antigens, ESAT-6/CFP-10/Rv3615c (75 %; IC95 % 34.9–96.8), and the purified protein derivative (87.5 %; IC 95 % 47.4–99.7) (p < 0.05)). Animals from a bTB free area showed no response against PhoP when analyzed by IGRA. Although, the humoral response detected 62.5 % (CI95% 24.5–91.5) of naturally infected animals, there was 100 % cross-reactivity among TB-free cattle. These results suggest that the PhoP protein is not a promising candidate for bTB diagnosis, due to it had relatively low levels of test sensitivity in the IGRA test, and very low specificity in a humoral antibody western blot assay.
publishDate 2025
dc.date.none.fl_str_mv 2025-02-28T10:36:31Z
2025-02-28T10:36:31Z
2025-03
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/20.500.12123/21501
https://www.sciencedirect.com/science/article/abs/pii/S0034528824003801
1532-2661
https://doi.org/10.1016/j.rvsc.2024.105513
url http://hdl.handle.net/20.500.12123/21501
https://www.sciencedirect.com/science/article/abs/pii/S0034528824003801
https://doi.org/10.1016/j.rvsc.2024.105513
identifier_str_mv 1532-2661
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repograntAgreement/INTA/2023-PD-L06-I114, Desarrollo y aplicación de métodos diagnósticos y epidemiológicos para la producción pecuaria sustentable y agroalimentaria en humanos con foco en Una Salud
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 184 : 105513 (March 2025)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
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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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