tuberculosis, M. bovis and BCG, but not in M. avium or M. smegmatis [18]. This suggests that the two-component system MtrAB might contribute

to the virulence of the M. tuberculosis complex through selective regulation of dnaA gene expression. A parallel study [13] has identified a “”GTCACAgcg”" motif for the recognition of MtrA in the fbpB promoter and the origin of replication. Interestingly, there exists a common conserved core sequence between the 9 bp motif and the motif identified within the dnaA promoter in the current study. Using a MalE-EnvZ kinase, but not the cognate partner kinase of MtrB, Rajagopalan et al suggested that the phosphorylation of MtrA had distinct regulation capacities. However, only 5% of the MtrA protein was shown to be phosphorylated [13]. In the present study, Etomoxir efforts to phosphorylate MtrA using the Batimastat mw EPZ015666 nmr partner kinase of MtrB failed (data not shown). Importantly, using several different methods, we showed that the nonphosphorylated MtrA could bind to the target DNA very well, suggesting that the form of MtrA might be involved in regulating the expression of its target genes. Obviously, the regulation mechanism of MtrAB needs to be further addressed in the future. Attempts to disrupt the mtrA gene in M. tuberculosis have been unsuccessful; thus, mtrA seems to be an essential gene for

M. tuberculosis proliferation [11]. The genes encoding the MtrAB two-component system of C. glutamicum were deleted successfully, and

this deletion strongly influenced the cell morphology, antibiotic susceptibility, and expression of genes involved in osmoprotection [15]. In the current study, a large group of target genes for MtrA was characterized from the genomes of both M. tuberculosis and M. smegmatis, including multiple transcriptional factors such as TetR family regulators, stress gene family protein (MSMEG_3308), and the isoniazid inducible protein IniA (MSMEG_0695). Inhibition of the mtrA gene, therefore, resulted in corresponding expression changes in many or all of these Carnitine palmitoyltransferase II target genes in M. smegmatis (Fig. 5C). In the current study, we found the conserved motifs of the MtrAB two-component system upstream of a large list of genes that have several different functions, including cell cycle progression regulation, secreted antigen, and drug resistance. Interestingly, as shown in Additional file 6, there are 42 genes (10%) that were found in both mycobacterial species. MtrA was reported to be involved in the transcriptional regulation of dnaA in M. tuberculosis; this provides the first direct evidence of its role in cell cycle progression [12]. In M. avium, MtrAB could respond to general stresses and ultimately inhibit cell division [14]. A recent study found that the promoter for immunodominant secreted antigen 85B was also characterized as the targets of MtrA [13]. Therefore, our findings were consistent with these previous studies.