Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis

Autores
Forrellad, Marina Andrea; Bianco, María Verónica; Blanco, Federico Carlos; Núñez García, Javier Luis Mariano; Klepp, Laura Ines; Vazquez, Cristina; Santangelo, María de la Paz; Rocha, Valeria; Soria, Marcelo; Golby, Paul; Gutierrez, Maximiliano; Bigi, Fabiana
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Tuberculosis is one of the leading causes of mortality throughout the world. Mycobacterium tuberculosis, the agent of human tuberculosis, has developed strategies involving proteins and other compounds called virulence factors to subvert human host defences and damage and invade the human host. Among these virulence-related proteins are the Mce proteins, which are encoded in the mce1, mce2, mce3 and mce4 operons of M. tuberculosis. The expression of the mce2 operon is negatively regulated by the Mce2R transcriptional repressor. Here we evaluated the role of Mce2R during the infection of M. tuberculosis in mice and macrophages and defined the genes whose expression is in vitro regulated by this transcriptional repressor. Results: We used a specialized transduction method for generating a mce2R mutant of M. tuberculosis H37Rv. Although we found equivalent replication of the MtΔmce2R mutant and the wild type strains in mouse lungs, overexpression of Mce2R in the complemented strain (MtΔmce2RComp) significantly impaired its replication. During in vitro infection of macrophages, we observed a significantly increased association of the late endosomal marker LAMP-2 to MtΔmce2RComp-containing phagosomes as compared to MtΔmce2R and the wild type strains. Whole transcriptional analysis showed that Mce2R regulates mainly the expression of the mce2 operon, in the in vitro conditions studied. Conclusions: The findings of the current study indicate that Mce2R weakly represses the in vivo expression of the mce2 operon in the studied conditions and argue for a role of the proteins encoded in Mce2R regulon in the arrest of phagosome maturation induced by M. tuberculosis.
Fil: Forrellad, Marina Andrea. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Instituto Nacional de Tecnología Agropecuaria; Argentina
Fil: Bianco, María Verónica. Instituto Nacional de Tecnología Agropecuaria; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina
Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina
Fil: Núñez García, Javier Luis Mariano. Animal Health Veterinary Laboratories Agency; Reino Unido
Fil: Klepp, Laura Ines. Instituto Nacional de Tecnología Agropecuaria; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina
Fil: Vazquez, Cristina. Helmholtz Centre For Infection Research; Alemania
Fil: Santangelo, María de la Paz. Instituto Nacional de Tecnología Agropecuaria; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina
Fil: Rocha, Valeria. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Instituto Nacional de Tecnología Agropecuaria; Argentina
Fil: Soria, Marcelo. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Biología Aplicada y Alimentos. Cátedra de Microbiología Agrícola; Argentina
Fil: Golby, Paul. Animal Health Veterinary Laboratories Agency; Reino Unido
Fil: Gutierrez, Maximiliano. Helmholtz Centre For Infection Research; Alemania
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina
Materia
MYCOBACTERIUM
TUBERCULOSIS
MCE2R
VIRULENCE
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:11336/103838
Acceder
id CONICETDig_8213513e530c4670cc754412fb4ee98b
oai_identifier_str oai:ri.conicet.gov.ar:11336/103838
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosisForrellad, Marina AndreaBianco, María VerónicaBlanco, Federico CarlosNúñez García, Javier Luis MarianoKlepp, Laura InesVazquez, CristinaSantangelo, María de la PazRocha, ValeriaSoria, MarceloGolby, PaulGutierrez, MaximilianoBigi, FabianaMYCOBACTERIUMTUBERCULOSISMCE2RVIRULENCEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: Tuberculosis is one of the leading causes of mortality throughout the world. Mycobacterium tuberculosis, the agent of human tuberculosis, has developed strategies involving proteins and other compounds called virulence factors to subvert human host defences and damage and invade the human host. Among these virulence-related proteins are the Mce proteins, which are encoded in the mce1, mce2, mce3 and mce4 operons of M. tuberculosis. The expression of the mce2 operon is negatively regulated by the Mce2R transcriptional repressor. Here we evaluated the role of Mce2R during the infection of M. tuberculosis in mice and macrophages and defined the genes whose expression is in vitro regulated by this transcriptional repressor. Results: We used a specialized transduction method for generating a mce2R mutant of M. tuberculosis H37Rv. Although we found equivalent replication of the MtΔmce2R mutant and the wild type strains in mouse lungs, overexpression of Mce2R in the complemented strain (MtΔmce2RComp) significantly impaired its replication. During in vitro infection of macrophages, we observed a significantly increased association of the late endosomal marker LAMP-2 to MtΔmce2RComp-containing phagosomes as compared to MtΔmce2R and the wild type strains. Whole transcriptional analysis showed that Mce2R regulates mainly the expression of the mce2 operon, in the in vitro conditions studied. Conclusions: The findings of the current study indicate that Mce2R weakly represses the in vivo expression of the mce2 operon in the studied conditions and argue for a role of the proteins encoded in Mce2R regulon in the arrest of phagosome maturation induced by M. tuberculosis.Fil: Forrellad, Marina Andrea. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Bianco, María Verónica. Instituto Nacional de Tecnología Agropecuaria; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; ArgentinaFil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; ArgentinaFil: Núñez García, Javier Luis Mariano. Animal Health Veterinary Laboratories Agency; Reino UnidoFil: Klepp, Laura Ines. Instituto Nacional de Tecnología Agropecuaria; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; ArgentinaFil: Vazquez, Cristina. Helmholtz Centre For Infection Research; AlemaniaFil: Santangelo, María de la Paz. Instituto Nacional de Tecnología Agropecuaria; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; ArgentinaFil: Rocha, Valeria. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Soria, Marcelo. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Biología Aplicada y Alimentos. Cátedra de Microbiología Agrícola; ArgentinaFil: Golby, Paul. Animal Health Veterinary Laboratories Agency; Reino UnidoFil: Gutierrez, Maximiliano. Helmholtz Centre For Infection Research; AlemaniaFil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; ArgentinaBioMed Central2013-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/103838Forrellad, Marina Andrea; Bianco, María Verónica; Blanco, Federico Carlos; Núñez García, Javier Luis Mariano; Klepp, Laura Ines; et al.; Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis; BioMed Central; BMC Microbiology; 13; 200; 7-2013; 1-91471-2180CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.biomedcentral.com/content/pdf/1471-2180-13-200.pdfinfo:eu-repo/semantics/altIdentifier/doi/10.1186/1471-2180-13-200info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:08Zoai:ri.conicet.gov.ar:11336/103838instacron: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:34982025-09-03 09:44:09.124CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis
title Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis
spellingShingle Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis
Forrellad, Marina Andrea
MYCOBACTERIUM
TUBERCULOSIS
MCE2R
VIRULENCE
title_short Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis
title_full Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis
title_fullStr Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis
title_full_unstemmed Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis
title_sort Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis
dc.creator.none.fl_str_mv Forrellad, Marina Andrea
Bianco, María Verónica
Blanco, Federico Carlos
Núñez García, Javier Luis Mariano
Klepp, Laura Ines
Vazquez, Cristina
Santangelo, María de la Paz
Rocha, Valeria
Soria, Marcelo
Golby, Paul
Gutierrez, Maximiliano
Bigi, Fabiana
author Forrellad, Marina Andrea
author_facet Forrellad, Marina Andrea
Bianco, María Verónica
Blanco, Federico Carlos
Núñez García, Javier Luis Mariano
Klepp, Laura Ines
Vazquez, Cristina
Santangelo, María de la Paz
Rocha, Valeria
Soria, Marcelo
Golby, Paul
Gutierrez, Maximiliano
Bigi, Fabiana
author_role author
author2 Bianco, María Verónica
Blanco, Federico Carlos
Núñez García, Javier Luis Mariano
Klepp, Laura Ines
Vazquez, Cristina
Santangelo, María de la Paz
Rocha, Valeria
Soria, Marcelo
Golby, Paul
Gutierrez, Maximiliano
Bigi, Fabiana
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MYCOBACTERIUM
TUBERCULOSIS
MCE2R
VIRULENCE
topic MYCOBACTERIUM
TUBERCULOSIS
MCE2R
VIRULENCE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background: Tuberculosis is one of the leading causes of mortality throughout the world. Mycobacterium tuberculosis, the agent of human tuberculosis, has developed strategies involving proteins and other compounds called virulence factors to subvert human host defences and damage and invade the human host. Among these virulence-related proteins are the Mce proteins, which are encoded in the mce1, mce2, mce3 and mce4 operons of M. tuberculosis. The expression of the mce2 operon is negatively regulated by the Mce2R transcriptional repressor. Here we evaluated the role of Mce2R during the infection of M. tuberculosis in mice and macrophages and defined the genes whose expression is in vitro regulated by this transcriptional repressor. Results: We used a specialized transduction method for generating a mce2R mutant of M. tuberculosis H37Rv. Although we found equivalent replication of the MtΔmce2R mutant and the wild type strains in mouse lungs, overexpression of Mce2R in the complemented strain (MtΔmce2RComp) significantly impaired its replication. During in vitro infection of macrophages, we observed a significantly increased association of the late endosomal marker LAMP-2 to MtΔmce2RComp-containing phagosomes as compared to MtΔmce2R and the wild type strains. Whole transcriptional analysis showed that Mce2R regulates mainly the expression of the mce2 operon, in the in vitro conditions studied. Conclusions: The findings of the current study indicate that Mce2R weakly represses the in vivo expression of the mce2 operon in the studied conditions and argue for a role of the proteins encoded in Mce2R regulon in the arrest of phagosome maturation induced by M. tuberculosis.
Fil: Forrellad, Marina Andrea. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Instituto Nacional de Tecnología Agropecuaria; Argentina
Fil: Bianco, María Verónica. Instituto Nacional de Tecnología Agropecuaria; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina
Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina
Fil: Núñez García, Javier Luis Mariano. Animal Health Veterinary Laboratories Agency; Reino Unido
Fil: Klepp, Laura Ines. Instituto Nacional de Tecnología Agropecuaria; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina
Fil: Vazquez, Cristina. Helmholtz Centre For Infection Research; Alemania
Fil: Santangelo, María de la Paz. Instituto Nacional de Tecnología Agropecuaria; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina
Fil: Rocha, Valeria. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Instituto Nacional de Tecnología Agropecuaria; Argentina
Fil: Soria, Marcelo. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Biología Aplicada y Alimentos. Cátedra de Microbiología Agrícola; Argentina
Fil: Golby, Paul. Animal Health Veterinary Laboratories Agency; Reino Unido
Fil: Gutierrez, Maximiliano. Helmholtz Centre For Infection Research; Alemania
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina
description Background: Tuberculosis is one of the leading causes of mortality throughout the world. Mycobacterium tuberculosis, the agent of human tuberculosis, has developed strategies involving proteins and other compounds called virulence factors to subvert human host defences and damage and invade the human host. Among these virulence-related proteins are the Mce proteins, which are encoded in the mce1, mce2, mce3 and mce4 operons of M. tuberculosis. The expression of the mce2 operon is negatively regulated by the Mce2R transcriptional repressor. Here we evaluated the role of Mce2R during the infection of M. tuberculosis in mice and macrophages and defined the genes whose expression is in vitro regulated by this transcriptional repressor. Results: We used a specialized transduction method for generating a mce2R mutant of M. tuberculosis H37Rv. Although we found equivalent replication of the MtΔmce2R mutant and the wild type strains in mouse lungs, overexpression of Mce2R in the complemented strain (MtΔmce2RComp) significantly impaired its replication. During in vitro infection of macrophages, we observed a significantly increased association of the late endosomal marker LAMP-2 to MtΔmce2RComp-containing phagosomes as compared to MtΔmce2R and the wild type strains. Whole transcriptional analysis showed that Mce2R regulates mainly the expression of the mce2 operon, in the in vitro conditions studied. Conclusions: The findings of the current study indicate that Mce2R weakly represses the in vivo expression of the mce2 operon in the studied conditions and argue for a role of the proteins encoded in Mce2R regulon in the arrest of phagosome maturation induced by M. tuberculosis.
publishDate 2013
dc.date.none.fl_str_mv 2013-07
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/11336/103838
Forrellad, Marina Andrea; Bianco, María Verónica; Blanco, Federico Carlos; Núñez García, Javier Luis Mariano; Klepp, Laura Ines; et al.; Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis; BioMed Central; BMC Microbiology; 13; 200; 7-2013; 1-9
1471-2180
CONICET Digital
CONICET
url http://hdl.handle.net/11336/103838
identifier_str_mv Forrellad, Marina Andrea; Bianco, María Verónica; Blanco, Federico Carlos; Núñez García, Javier Luis Mariano; Klepp, Laura Ines; et al.; Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis; BioMed Central; BMC Microbiology; 13; 200; 7-2013; 1-9
1471-2180
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1186/1471-2180-13-200
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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application/pdf
application/pdf
application/pdf
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dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
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reponame_str CONICET Digital (CONICET)
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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
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