Role of IdeR and HupB in the regulation of the mbt biosynthetic machinery in M. tuberculosis and the sequence of events occurring under high- and low-iron conditions. (A) Using mbtB as the representative gene for the mbt operon, the events occurring under high-iron conditions are represented. When iron is present in sufficient amounts (≥200 μM), there is no transcription of mbtB, as the IdeR-Fe2+ complex that is formed occupies the 19-bp IdeR box in close vicinity of the transcriptional start point (TSP). HupB is not expressed under these conditions. (B) Sequence of events that occur when the iron levels begin to fall. IdeR is unable to form the IdeR-Fe2+ complex in the presence of decreasing levels of iron, and the induced HupB, detectable at 144 μM iron, now can bind the HupB box in the presence of available iron (it can bind even at 25 μM, as shown in Fig. 5). The empty IdeR box and the presence of HupB at the HupB box, located upstream of the IdeR box, favors transcription of mbtB by RNA polymerase (RNAP).