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Open Access Research article

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

Marina Andrea Forrellad1, María Verónica Bianco1, Federico Carlos Blanco1, Javier Nuñez2, Laura Inés Klepp1, Cristina Lourdes Vazquez3, María de la Paz Santangelo1, Rosana Valeria Rocha1, Marcelo Soria4, Paul Golby2, Maximiliano Gabriel Gutierrez35 and Fabiana Bigi1*

Author Affiliations

1 Instituto de Biotecnología, CICVyA-INTA, N. Repetto and De los Reseros, Hurlingham 1686, Argentina

2 Animal Health Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB, UK

3 Research Group Phagosome Biology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, Braunschweig 38124, Germany

4 Microbiología Agrícola Facultad de Agronomía, Universidad de Buenos Aires, Avenue San Martín 4453, Buenos Aires 1417, Argentina

5 Present address: Division of Mycobacterial Research, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK

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BMC Microbiology 2013, 13:200  doi:10.1186/1471-2180-13-200

Published: 5 September 2013

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.

Keywords:
Mycobacterium tuberculosis; mce2R; Phagosome arresting