Effect of the deletion of lprG and p55 genes in the K10 strain of Mycobacterium avium subspecies paratuberculosis

Autores: Viale, Mariana; Colombatti Olivieri, Maria Alejandra; Alonso, Maria Natalia; Moyano, Roberto Damian; Imperiale, Belén Rocío; Morcillo, Nora Susana; Santangelo, María De La Paz; Davis, William; Romano, Maria Isabel
Año de publicación: 2021
Idioma: inglés
Tipo de recurso: artículo
Estado: versión publicada
Descripción: The lprG-p55 operon of Mycobacterium tuberculosis, M. bovis and M. avium strain D4ER has been identified as a virulence factor involved in the transport of toxic compounds. LprG is a lipoprotein that modulates the host immune response against mycobacteria, whereas P55 is an efflux pump that provides resistance to several drugs. In the present study we search for, and characterize, lprg and p55, putative virulence genes in Mycobacterium avium subsp. paratuberculosis (MAP) to generate a live-attenuated strain of MAP that may be useful in the future as live-attenuated vaccine. For this purpose, we generated and evaluated two mutants of MAP strain K10: one mutant lacking the lprG gene (ΔlprG) and the other lacking both genes lprG and p55 (ΔlprG–p55). None of the mutant strains showed altered susceptibility to first-line and second-line antituberculosis drugs or ethidium bromide, only the double mutant had two-fold increase in clarithromycin susceptibility compared with the wild-type strain. The deletion of lprG and of lprG-p55 reduced the replication of MAP in bovine macrophages; however, only the mutant in lprG-p55 grew faster in liquid media and showed reduced viability in macrophages and in a mouse model. Considering that the deletion of both genes lprG-p55, but not that of lprG alone, showed a reduced replication in vivo, we can speculate that p55 contributes to the survival of MAP in this animal model.
Instituto de Biotecnología
Fil: Viale, Mariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Viale, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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: 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
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: Imperiale, Belén Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina
Fil: Imperiale, Belén Rocío. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Morcillo, Nora Susana. Provincia de Buenos Aires. Ministerio de Salud. Hospital "Dr. Antonio A. Cetrángolo"; Argentina
Fil: Santangelo, María De La Paz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Santangelo, María De La Paz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Davis, William. Washington State University. College of Veterinary Medicine. Department of Veterinary Microbiology and Pathology; Estados Unidos
Fil: Romano, Maria Isabel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Romano, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fuente: Research in Veterinary Science 138 : 1-10. (September 2021)
Materia: Mycobacterium avium subsp. paratuberculosis
Virulence
Immune Response
Lipoproteins
Animal Models
Virulencia
Respuesta Inmunológica
Lipoproteínas
Modelo Animal
Nivel de accesibilidad: acceso restringido
Condiciones de uso: http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
Institución: Instituto Nacional de Tecnología Agropecuaria
OAI Identificador: oai:localhost:20.500.12123/27111

Acceder

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spelling	Effect of the deletion of lprG and p55 genes in the K10 strain of Mycobacterium avium subspecies paratuberculosisViale, MarianaColombatti Olivieri, Maria AlejandraAlonso, Maria NataliaMoyano, Roberto DamianImperiale, Belén RocíoMorcillo, Nora SusanaSantangelo, María De La PazDavis, WilliamRomano, Maria IsabelMycobacterium avium subsp. paratuberculosisVirulenceImmune ResponseLipoproteinsAnimal ModelsVirulenciaRespuesta InmunológicaLipoproteínasModelo AnimalThe lprG-p55 operon of Mycobacterium tuberculosis, M. bovis and M. avium strain D4ER has been identified as a virulence factor involved in the transport of toxic compounds. LprG is a lipoprotein that modulates the host immune response against mycobacteria, whereas P55 is an efflux pump that provides resistance to several drugs. In the present study we search for, and characterize, lprg and p55, putative virulence genes in Mycobacterium avium subsp. paratuberculosis (MAP) to generate a live-attenuated strain of MAP that may be useful in the future as live-attenuated vaccine. For this purpose, we generated and evaluated two mutants of MAP strain K10: one mutant lacking the lprG gene (ΔlprG) and the other lacking both genes lprG and p55 (ΔlprG–p55). None of the mutant strains showed altered susceptibility to first-line and second-line antituberculosis drugs or ethidium bromide, only the double mutant had two-fold increase in clarithromycin susceptibility compared with the wild-type strain. The deletion of lprG and of lprG-p55 reduced the replication of MAP in bovine macrophages; however, only the mutant in lprG-p55 grew faster in liquid media and showed reduced viability in macrophages and in a mouse model. Considering that the deletion of both genes lprG-p55, but not that of lprG alone, showed a reduced replication in vivo, we can speculate that p55 contributes to the survival of MAP in this animal model.Instituto de BiotecnologíaFil: Viale, Mariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Viale, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: 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: 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; 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: Imperiale, Belén Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; ArgentinaFil: Imperiale, Belén Rocío. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Morcillo, Nora Susana. Provincia de Buenos Aires. Ministerio de Salud. Hospital "Dr. Antonio A. Cetrángolo"; ArgentinaFil: Santangelo, María De La Paz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Santangelo, María De La Paz. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Davis, William. Washington State University. College of Veterinary Medicine. Department of Veterinary Microbiology and Pathology; Estados UnidosFil: Romano, Maria Isabel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Romano, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier2026-07-23T12:26:09Z2026-07-23T12:26:09Z2021-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/27111https://www.sciencedirect.com/science/article/pii/S00345288210017390034-52881532-2661https://doi.org/10.1016/j.rvsc.2021.05.019Research in Veterinary Science 138 : 1-10. (September 2021)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repograntAgreement/INTA/PNBIO/1131034/AR./Inmunología molecular y genómica funcional aplicadas a interacciones patógeno hospedador de interés pecuario.info: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)2026-09-24T11:43:29Zoai:localhost:20.500.12123/27111instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2026-09-24 11:43:31.075INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv	Effect of the deletion of lprG and p55 genes in the K10 strain of Mycobacterium avium subspecies paratuberculosis
title	Effect of the deletion of lprG and p55 genes in the K10 strain of Mycobacterium avium subspecies paratuberculosis
spellingShingle	Effect of the deletion of lprG and p55 genes in the K10 strain of Mycobacterium avium subspecies paratuberculosis Viale, Mariana Mycobacterium avium subsp. paratuberculosis Virulence Immune Response Lipoproteins Animal Models Virulencia Respuesta Inmunológica Lipoproteínas Modelo Animal
title_short	Effect of the deletion of lprG and p55 genes in the K10 strain of Mycobacterium avium subspecies paratuberculosis
title_full	Effect of the deletion of lprG and p55 genes in the K10 strain of Mycobacterium avium subspecies paratuberculosis
title_fullStr	Effect of the deletion of lprG and p55 genes in the K10 strain of Mycobacterium avium subspecies paratuberculosis
title_full_unstemmed	Effect of the deletion of lprG and p55 genes in the K10 strain of Mycobacterium avium subspecies paratuberculosis
title_sort	Effect of the deletion of lprG and p55 genes in the K10 strain of Mycobacterium avium subspecies paratuberculosis
dc.creator.none.fl_str_mv	Viale, Mariana Colombatti Olivieri, Maria Alejandra Alonso, Maria Natalia Moyano, Roberto Damian Imperiale, Belén Rocío Morcillo, Nora Susana Santangelo, María De La Paz Davis, William Romano, Maria Isabel
author	Viale, Mariana
author_facet	Viale, Mariana Colombatti Olivieri, Maria Alejandra Alonso, Maria Natalia Moyano, Roberto Damian Imperiale, Belén Rocío Morcillo, Nora Susana Santangelo, María De La Paz Davis, William Romano, Maria Isabel
author_role	author
author2	Colombatti Olivieri, Maria Alejandra Alonso, Maria Natalia Moyano, Roberto Damian Imperiale, Belén Rocío Morcillo, Nora Susana Santangelo, María De La Paz Davis, William Romano, Maria Isabel
author2_role	author author author author author author author author
dc.subject.none.fl_str_mv	Mycobacterium avium subsp. paratuberculosis Virulence Immune Response Lipoproteins Animal Models Virulencia Respuesta Inmunológica Lipoproteínas Modelo Animal
topic	Mycobacterium avium subsp. paratuberculosis Virulence Immune Response Lipoproteins Animal Models Virulencia Respuesta Inmunológica Lipoproteínas Modelo Animal
dc.description.none.fl_txt_mv	The lprG-p55 operon of Mycobacterium tuberculosis, M. bovis and M. avium strain D4ER has been identified as a virulence factor involved in the transport of toxic compounds. LprG is a lipoprotein that modulates the host immune response against mycobacteria, whereas P55 is an efflux pump that provides resistance to several drugs. In the present study we search for, and characterize, lprg and p55, putative virulence genes in Mycobacterium avium subsp. paratuberculosis (MAP) to generate a live-attenuated strain of MAP that may be useful in the future as live-attenuated vaccine. For this purpose, we generated and evaluated two mutants of MAP strain K10: one mutant lacking the lprG gene (ΔlprG) and the other lacking both genes lprG and p55 (ΔlprG–p55). None of the mutant strains showed altered susceptibility to first-line and second-line antituberculosis drugs or ethidium bromide, only the double mutant had two-fold increase in clarithromycin susceptibility compared with the wild-type strain. The deletion of lprG and of lprG-p55 reduced the replication of MAP in bovine macrophages; however, only the mutant in lprG-p55 grew faster in liquid media and showed reduced viability in macrophages and in a mouse model. Considering that the deletion of both genes lprG-p55, but not that of lprG alone, showed a reduced replication in vivo, we can speculate that p55 contributes to the survival of MAP in this animal model. Instituto de Biotecnología Fil: Viale, Mariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina Fil: Viale, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina 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: 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 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: Imperiale, Belén Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina Fil: Imperiale, Belén Rocío. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Morcillo, Nora Susana. Provincia de Buenos Aires. Ministerio de Salud. Hospital "Dr. Antonio A. Cetrángolo"; Argentina Fil: Santangelo, María De La Paz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Santangelo, María De La Paz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Davis, William. Washington State University. College of Veterinary Medicine. Department of Veterinary Microbiology and Pathology; Estados Unidos Fil: Romano, Maria Isabel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina Fil: Romano, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description	The lprG-p55 operon of Mycobacterium tuberculosis, M. bovis and M. avium strain D4ER has been identified as a virulence factor involved in the transport of toxic compounds. LprG is a lipoprotein that modulates the host immune response against mycobacteria, whereas P55 is an efflux pump that provides resistance to several drugs. In the present study we search for, and characterize, lprg and p55, putative virulence genes in Mycobacterium avium subsp. paratuberculosis (MAP) to generate a live-attenuated strain of MAP that may be useful in the future as live-attenuated vaccine. For this purpose, we generated and evaluated two mutants of MAP strain K10: one mutant lacking the lprG gene (ΔlprG) and the other lacking both genes lprG and p55 (ΔlprG–p55). None of the mutant strains showed altered susceptibility to first-line and second-line antituberculosis drugs or ethidium bromide, only the double mutant had two-fold increase in clarithromycin susceptibility compared with the wild-type strain. The deletion of lprG and of lprG-p55 reduced the replication of MAP in bovine macrophages; however, only the mutant in lprG-p55 grew faster in liquid media and showed reduced viability in macrophages and in a mouse model. Considering that the deletion of both genes lprG-p55, but not that of lprG alone, showed a reduced replication in vivo, we can speculate that p55 contributes to the survival of MAP in this animal model.
publishDate	2021
dc.date.none.fl_str_mv	2021-09 2026-07-23T12:26:09Z 2026-07-23T12:26:09Z
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
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dc.identifier.none.fl_str_mv	http://hdl.handle.net/20.500.12123/27111 https://www.sciencedirect.com/science/article/pii/S0034528821001739 0034-5288 1532-2661 https://doi.org/10.1016/j.rvsc.2021.05.019
url	http://hdl.handle.net/20.500.12123/27111 https://www.sciencedirect.com/science/article/pii/S0034528821001739 https://doi.org/10.1016/j.rvsc.2021.05.019
identifier_str_mv	0034-5288 1532-2661
dc.language.none.fl_str_mv	eng
language	eng
dc.relation.none.fl_str_mv	info:eu-repograntAgreement/INTA/PNBIO/1131034/AR./Inmunología molecular y genómica funcional aplicadas a interacciones patógeno hospedador de interés pecuario.
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dc.publisher.none.fl_str_mv	Elsevier
publisher.none.fl_str_mv	Elsevier
dc.source.none.fl_str_mv	Research in Veterinary Science 138 : 1-10. (September 2021) reponame:INTA Digital (INTA) instname:Instituto Nacional de Tecnología Agropecuaria
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Effect of the deletion of lprG and p55 genes in the K10 strain of Mycobacterium avium subspecies paratuberculosis

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