Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis
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 huma...
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| Format: | Artículo |
| Language: | Inglés |
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BMC
2019
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| Online Access: | 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 |
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| author | 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_browse | Bianco, María Veronica Bigi, Fabiana Blanco, Federico Carlos Forrellad, Marina Andrea Golby, Paul Gutierrez, Maximiliano Gabriel Klepp, Laura Ines Nuñez, Javier Rocha, Rosana Valeria Santangelo, María De La Paz Soria, Marcelo Vazquez, Cristina Lourdes |
| 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_sort | Forrellad, Marina Andrea |
| collection | INTA Digital |
| 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. |
| format | Artículo |
| id | INTA4265 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2019 |
| publishDateRange | 2019 |
| publishDateSort | 2019 |
| publisher | BMC |
| publisherStr | BMC |
| record_format | dspace |
| spelling | INTA42652019-01-15T12:11:15Z Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis 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 Mycobacterium tuberculosis Enfermedades Humanas Tuberculosis Experimentación en Laboratorio Proteínas Human Diseases Laboratory Experimentation Proteins 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 2019-01-15T12:06:03Z 2019-01-15T12:06:03Z 2013-09 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 eng 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) application/pdf BMC BMC Microbiology 13 : 200 (2013) |
| spellingShingle | Mycobacterium tuberculosis Enfermedades Humanas Tuberculosis Experimentación en Laboratorio Proteínas Human Diseases Laboratory Experimentation Proteins 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 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 |
| 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_short | 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 |
| topic | Mycobacterium tuberculosis Enfermedades Humanas Tuberculosis Experimentación en Laboratorio Proteínas Human Diseases Laboratory Experimentation Proteins |
| 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 |
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