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Background  The two-component systems of  Mycobacterium tuberculosis  are apparently required for its growth and resistance in hostile host environments. In such environments, MtrAB has been reported to regulate the expression of the  M. tuberculosis  replication initiator gene,  dnaA . However, the  dnaA  promoter binding sites and many potential target genes for MtrA have yet to be precisely characterized.    Results  In this study, a 7 bp sequence motif in the  dnaA  promoter region was identified for MtrA binding using DNaseI footprinting assays and surface plasmon resonance (SPR) analysis. Approximately 420 target genes potentially regulated by MtrA, including the isoniazid inducible gene  iniB , were further characterized from  M. tuberculosis  and  M. smegmatis  genomes. When assayed using quantitative real-time PCR (qRT-PCR), many of the target genes demonstrated significant expression changes when the antisense mRNA of the  mtrA  gene was expressed in  M. smegmatis . The recombinant mycobacteria grew in length and were more sensitive to two anti-tuberculosis drugs, isoniazid and streptomycin.    Conclusions  These findings yield critical information about the regulatory mechanisms of the MtrAB two-component system and its role in the drug resistance of  M. smegmatis .

bmc microbiology

The characterization of conserved binding motifs and potential target genes for M. tuberculosis MtrAB reveals a link between the two-component system and the drug resistance of M. smegmatis