Background: Tuberculosis is one of the leading causes of mortality throughout the world. Mycobacterium\r\ntuberculosis, the agent of human tuberculosis, has developed strategies involving proteins and other compounds\r\ncalled virulence factors to subvert human host defences and damage and invade the human host. Among these\r\nvirulence-related proteins are the Mce proteins, which are encoded in the mce1, mce2, mce3 and mce4 operons of\r\nM. tuberculosis. The expression of the mce2 operon is negatively regulated by the Mce2R transcriptional repressor.\r\nHere we evaluated the role of Mce2R during the infection of M. tuberculosis in mice and macrophages and defined\r\nthe genes whose expression is in vitro regulated by this transcriptional repressor.\r\nResults: We used a specialized transduction method for generating a mce2R mutant of M. tuberculosis H37Rv.\r\nAlthough we found equivalent replication of the Mt?mce2R mutant and the wild type strains in mouse lungs,\r\noverexpression of Mce2R in the complemented strain (Mt?mce2RComp) significantly impaired its replication.\r\nDuring in vitro infection of macrophages, we observed a significantly increased association of the late endosomal\r\nmarker LAMP-2 to Mt?mce2RComp-containing phagosomes as compared to Mt?mce2R and the wild type strains.\r\nWhole transcriptional analysis showed that Mce2R regulates mainly the expression of the mce2 operon, in the\r\nin vitro conditions studied.\r\nConclusions: The findings of the current study indicate that Mce2R weakly represses the in vivo expression of the\r\nmce2 operon in the studied conditions and argue for a role of the proteins encoded in Mce2R regulon in the arrest\r\nof phagosome maturation induced by M. tuberculosis.
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