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

Autores
Forrellad, Marina Andrea; Bianco, María Veronica; Blanco, Federico Carlos; Nuñez, Javier; Klepp, Laura Ines; Vazquez, Cristina Lourdes; Santangelo, María De La Paz; Rocha, Rosana Valeria; Soria, Marcelo; Golby, Paul; Gutierrez, Maximiliano Gabriel; 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.
Instituto de Biotecnología
Fil: Forrellad, Marina Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Bianco, María Veronica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Nuñez, Javier. Animal Health Veterinary Laboratories Agency; Reino Unidos
Fil: Klepp, Laura Ines. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Vazquez, Cristina Lourdes. Helmholtz Centre for Infection Research. Research Group Phagosome Biology; Alemania
Fil: Santangelo, María De La Paz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Rocha, Rosana Valeria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Soria, Marcelo. Universidad de Buenos Aires. Facultad de Agronomía. Cátedra de Microbiología Agrícola; Argentina
Fil: Golby, Paul. Animal Health Veterinary Laboratories Agency; Reino Unidos
Fil: Gutierrez, Maximiliano Gabriel. Helmholtz Centre for Infection Research. Research Group Phagosome Biology; Alemania. MRC National Institute for Medical Research. Division of Mycobacterial Research; Reino Unido
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fuente
BMC Microbiology 13 : 200 (2013)
Materia
Mycobacterium tuberculosis
Enfermedades Humanas
Tuberculosis
Experimentación en Laboratorio
Proteínas
Human Diseases
Laboratory Experimentation
Proteins
Nivel de accesibilidad
acceso abierto
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:20.500.12123/4265
Acceder
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oai_identifier_str oai:localhost:20.500.12123/4265
network_acronym_str INTADig
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network_name_str INTA Digital (INTA)
spelling Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosisForrellad, Marina AndreaBianco, María VeronicaBlanco, Federico CarlosNuñez, JavierKlepp, Laura InesVazquez, Cristina LourdesSantangelo, María De La PazRocha, Rosana ValeriaSoria, MarceloGolby, PaulGutierrez, Maximiliano GabrielBigi, FabianaMycobacterium tuberculosisEnfermedades HumanasTuberculosisExperimentación en LaboratorioProteínasHuman DiseasesLaboratory ExperimentationProteinsBackground: 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.Instituto de BiotecnologíaFil: Forrellad, Marina Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Bianco, María Veronica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Nuñez, Javier. Animal Health Veterinary Laboratories Agency; Reino UnidosFil: Klepp, Laura Ines. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Vazquez, Cristina Lourdes. Helmholtz Centre for Infection Research. Research Group Phagosome Biology; AlemaniaFil: Santangelo, María De La Paz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Rocha, Rosana Valeria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Soria, Marcelo. Universidad de Buenos Aires. Facultad de Agronomía. Cátedra de Microbiología Agrícola; ArgentinaFil: Golby, Paul. Animal Health Veterinary Laboratories Agency; Reino UnidosFil: Gutierrez, Maximiliano Gabriel. Helmholtz Centre for Infection Research. Research Group Phagosome Biology; Alemania. MRC National Institute for Medical Research. Division of Mycobacterial Research; Reino UnidoFil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaBMC2019-01-15T12:06:03Z2019-01-15T12:06:03Z2013-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://bmcmicrobiol.biomedcentral.com/articles/10.1186/1471-2180-13-200http://hdl.handle.net/20.500.12123/42651471-2180https://doi.org/10.1186/1471-2180-13-200BMC Microbiology 13 : 200 (2013)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-10-16T09:29:25Zoai:localhost:20.500.12123/4265instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-10-16 09:29:25.5INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
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
Enfermedades Humanas
Tuberculosis
Experimentación en Laboratorio
Proteínas
Human Diseases
Laboratory Experimentation
Proteins
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 Veronica
Blanco, Federico Carlos
Nuñez, Javier
Klepp, Laura Ines
Vazquez, Cristina Lourdes
Santangelo, María De La Paz
Rocha, Rosana Valeria
Soria, Marcelo
Golby, Paul
Gutierrez, Maximiliano Gabriel
Bigi, Fabiana
author Forrellad, Marina Andrea
author_facet Forrellad, Marina Andrea
Bianco, María Veronica
Blanco, Federico Carlos
Nuñez, Javier
Klepp, Laura Ines
Vazquez, Cristina Lourdes
Santangelo, María De La Paz
Rocha, Rosana Valeria
Soria, Marcelo
Golby, Paul
Gutierrez, Maximiliano Gabriel
Bigi, Fabiana
author_role author
author2 Bianco, María Veronica
Blanco, Federico Carlos
Nuñez, Javier
Klepp, Laura Ines
Vazquez, Cristina Lourdes
Santangelo, María De La Paz
Rocha, Rosana Valeria
Soria, Marcelo
Golby, Paul
Gutierrez, Maximiliano Gabriel
Bigi, Fabiana
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mycobacterium tuberculosis
Enfermedades Humanas
Tuberculosis
Experimentación en Laboratorio
Proteínas
Human Diseases
Laboratory Experimentation
Proteins
topic Mycobacterium tuberculosis
Enfermedades Humanas
Tuberculosis
Experimentación en Laboratorio
Proteínas
Human Diseases
Laboratory Experimentation
Proteins
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.
Instituto de Biotecnología
Fil: Forrellad, Marina Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Bianco, María Veronica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Nuñez, Javier. Animal Health Veterinary Laboratories Agency; Reino Unidos
Fil: Klepp, Laura Ines. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Vazquez, Cristina Lourdes. Helmholtz Centre for Infection Research. Research Group Phagosome Biology; Alemania
Fil: Santangelo, María De La Paz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Rocha, Rosana Valeria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Soria, Marcelo. Universidad de Buenos Aires. Facultad de Agronomía. Cátedra de Microbiología Agrícola; Argentina
Fil: Golby, Paul. Animal Health Veterinary Laboratories Agency; Reino Unidos
Fil: Gutierrez, Maximiliano Gabriel. Helmholtz Centre for Infection Research. Research Group Phagosome Biology; Alemania. MRC National Institute for Medical Research. Division of Mycobacterial Research; Reino Unido
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). 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 2013-09
2019-01-15T12:06:03Z
2019-01-15T12:06:03Z
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 https://bmcmicrobiol.biomedcentral.com/articles/10.1186/1471-2180-13-200
http://hdl.handle.net/20.500.12123/4265
1471-2180
https://doi.org/10.1186/1471-2180-13-200
url https://bmcmicrobiol.biomedcentral.com/articles/10.1186/1471-2180-13-200
http://hdl.handle.net/20.500.12123/4265
https://doi.org/10.1186/1471-2180-13-200
identifier_str_mv 1471-2180
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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 openAccess
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 BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv BMC Microbiology 13 : 200 (2013)
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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