Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis
| العنوان: | Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis |
|---|---|
| المؤلفون: | Cristina Lourdes Vázquez, Marina Andrea Forrellad, Federico Carlos Blanco, Rosana Valeria Rocha, María de la Paz Santangelo, Marcelo Abel Soria, Paul Golby, María Verónica Bianco, Fabiana Bigi, Maximiliano G. Gutierrez, Laura Inés Klepp, Javier Nunez |
| المصدر: | BMC Microbiology CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Vol. 13, no. 1 FAUBA Digital (UBA-FAUBA) Universidad de Buenos Aires. Facultad de Agronomía instacron:UBA-FAUBA Vol.13, no.1 13:200 BMC Microbiology 13 : 200 (2013) INTA Digital (INTA) Instituto Nacional de Tecnología Agropecuaria instacron:INTA |
| بيانات النشر: | BioMed Central, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Operon, REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION, purl.org/becyt/ford/1 [https], Mice, Transduction, Genetic, Transcriptional regulation, OPERON, mce2R, Lung, WILD TYPE, Phagosome, Mice, Inbred BALB C, 0303 health sciences, Enfermedades Humanas, Human Diseases, MUS, 3. Good health, Laboratory Experimentation, PHAGOSOME, Proteínas, CIENCIAS NATURALES Y EXACTAS, Research Article, Microbiology (medical), Experimentación en Laboratorio, Virulence Factors, Repressor, Biology, TUBERCULOSIS, Microbiology, Mycobacterium tuberculosis, Ciencias Biológicas, 03 medical and health sciences, Bacterial Proteins, Biología Celular, Microbiología, Phagosome maturation, NONHUMAN, Animals, Tuberculosis, purl.org/becyt/ford/1.6 [https], REGULON, 030304 developmental biology, IN VIVO STUDY, MYCOBACTERIUM TUBERCULOSIS, Antigens, Bacterial, 030306 microbiology, MORTALITY, Gene Expression Profiling, Macrophages, Wild type, Proteins, MYCOBACTERIUM, Gene Expression Regulation, Bacterial, biology.organism_classification, MCE2R, Repressor Proteins, Disease Models, Animal, Regulon, Phagosome arresting, VIRULENCE, PHAGOSOME ARRESTING, HOST RESISTANCE, MACROPHAGE, Gene Deletion, BACTERIAL VIRULENCE |
| الوصف: | 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 |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24f2880f4839ba9f83c07fab2a59fb1fTest http://www.biomedcentral.com/content/pdf/1471-2180-13-200.pdfTest |
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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. 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[SubjectFull] => HOST RESISTANCE
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[61] => Array
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[SubjectFull] => MACROPHAGE
[Type] => general
)
[62] => Array
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[SubjectFull] => Gene Deletion
[Type] => general
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[63] => Array
(
[SubjectFull] => BACTERIAL VIRULENCE
[Type] => general
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[Titles] => Array
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[0] => Array
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[TitleFull] => Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis
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[Name] => Array
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[PersonEntity] => Array
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[Name] => Array
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[PersonEntity] => Array
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[Name] => Array
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[4] => Array
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[PersonEntity] => Array
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[Name] => Array
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[NameFull] => Marcelo Abel Soria
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[PersonEntity] => Array
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[Name] => Array
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[NameFull] => Paul Golby
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[7] => Array
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[PersonEntity] => Array
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[Name] => Array
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[NameFull] => María Verónica Bianco
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[PersonEntity] => Array
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[Name] => Array
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[NameFull] => Fabiana Bigi
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[9] => Array
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[PersonEntity] => Array
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[Name] => Array
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[NameFull] => Maximiliano G. Gutierrez
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[10] => Array
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[PersonEntity] => Array
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[Name] => Array
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[NameFull] => Laura Inés Klepp
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[11] => Array
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[PersonEntity] => Array
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[Name] => Array
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[NameFull] => Javier Nunez
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[Type] => issn-locals
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|
| IllustrationInfo |