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

2.50
Hdl Handle:
http://hdl.handle.net/10033/621047
Title:
Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis
Authors:
Forrellad, Marina A; Bianco, María V; Blanco, Federico C; Nuñez, Javier; Klepp, Laura I; Vazquez, Cristina L; Santangelo, María d l P; Rocha, Rosana V; Soria, Marcelo; Golby, Paul; Gutierrez, Maximiliano G; Bigi, Fabiana
Abstract:
Abstract 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.
Citation:
BMC Microbiology. 2013 Sep 05;13(1):200
Issue Date:
5-Sep-2013
URI:
http://dx.doi.org/10.1186/1471-2180-13-200; http://hdl.handle.net/10033/621047
Type:
Journal Article
Appears in Collections:
Publications of the RG Phagosomen Biologie

Full metadata record

DC FieldValue Language
dc.contributor.authorForrellad, Marina Aen
dc.contributor.authorBianco, María Ven
dc.contributor.authorBlanco, Federico Cen
dc.contributor.authorNuñez, Javieren
dc.contributor.authorKlepp, Laura Ien
dc.contributor.authorVazquez, Cristina Len
dc.contributor.authorSantangelo, María d l Pen
dc.contributor.authorRocha, Rosana Ven
dc.contributor.authorSoria, Marceloen
dc.contributor.authorGolby, Paulen
dc.contributor.authorGutierrez, Maximiliano Gen
dc.contributor.authorBigi, Fabianaen
dc.date.accessioned2017-08-04T09:10:08Z-
dc.date.available2017-08-04T09:10:08Z-
dc.date.issued2013-09-05en
dc.identifier.citationBMC Microbiology. 2013 Sep 05;13(1):200en
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2180-13-200en
dc.identifier.urihttp://hdl.handle.net/10033/621047-
dc.description.abstractAbstract 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.en
dc.titleStudy of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosisen
dc.typeJournal Articleen
dc.language.rfc3066enen
dc.rights.holderForrellad et al.; licensee BioMed Central Ltd.en
dc.date.updated2015-09-04T08:22:30Zen
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