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Background  Pathogenic mycobacteria such as  M. tuberculosis ,  M. bovis  or  M. leprae  are characterised by their extremely slow growth rate which plays an important role in mycobacterial virulence and eradication of the bacteria. Various limiting factors influence the generation time of mycobacteria, and the mycobacterial DNA-binding protein 1 (MDP1) has also been implicated in growth regulation. Our strategy to investigate the role of MDP1 in mycobacterial growth consisted in the generation and characterisation of a  M. bovis  BCG derivative expressing a MDP1-antisense gene.    Results  The expression rate of the MDP1 protein in the recombinant  M. bovis  BCG containing the MDP1-antisense plasmid was reduced by about 50% compared to the reference strain  M. bovis  BCG containing the empty vector. In comparison to this reference strain, the recombinant  M. bovis  BCG grew faster in broth culture and reached higher cell masses in stationary phase. Likewise its intracellular growth in mouse and human macrophages was ameliorated. Bacterial clumping in broth culture was reduced by the antisense plasmid. The antisense plasmid increased the susceptibility of the bacteria towards Ampicillin. 2-D protein gels of bacteria maintained under oxygen-poor conditions demonstrated a reduction in the number and the intensity of many protein spots in the antisense strain compared to the reference strain.    Conclusion  The MDP1 protein has a major impact on various growth characteristics of  M. bovis  BCG. It plays an important role in virulence-related traits such as aggregate formation and intracellular multiplication. Its impact on the protein expression in a low-oxygen atmosphere indicates a role in the adaptation to the hypoxic conditions present in the granuloma.

The mycobacterial DNA-binding protein 1 (MDP1) from Mycobacterium bovis BCG influences various growth characteristics