title: Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis.
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.
authors.affiliation: Instituto de Biotecnología, CICVyA-INTA, N, Repetto and De los Reseros, Hurlingham 1686, Argentina. fbigi@cnia.inta.gov.ar.
authors.forename: Marina Andrea
authors.initials: MA
authors.lastname: Forrellad
authors.forename: María Verónica
authors.initials: MV
authors.lastname: Bianco
authors.forename: Federico Carlos
authors.initials: FC
authors.lastname: Blanco
authors.forename: Javier
authors.initials: J
authors.lastname: Nuñez
authors.forename: Laura Inés
authors.initials: LI
authors.lastname: Klepp
authors.forename: Cristina Lourdes
authors.initials: CL
authors.lastname: Vazquez
authors.forename: María de la Paz
authors.initials: Mde L
authors.lastname: Santangelo
authors.forename: Rosana Valeria
authors.initials: RV
authors.lastname: Rocha
authors.forename: Marcelo
authors.initials: M
authors.lastname: Soria
authors.forename: Paul
authors.initials: P
authors.lastname: Golby
authors.forename: Maximiliano Gabriel
authors.initials: MG
authors.lastname: Gutierrez
authors.forename: Fabiana
authors.initials: F
authors.lastname: Bigi
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000096:biosynthesis*; D004195:Disease Models, Animal; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D008168:Lung / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D009876:Operon; D012097:Repressor Proteins / Q000378:metabolism*; D014161:Transduction, Genetic; D014376:Tuberculosis / Q000382:microbiology / Q000473:pathology; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D012097:Repressor Proteins; D037521:Virulence Factors; C443482:mce2 protein, Mycobacterium tuberculosis