Although functional annotations on TFs are still limited, it is possible to classify the cross-regulating TFs into broad categories according to the physiological functions of the target structural genes: carbohydrate initial catabolism, respiration, biofilm formation and chemotaxis, etc. As shown in Fig. 1, these broad classes correspond to different local network topologies. Due to their contrasting topologies, in what follows, we will focus our discussion on short regulatory cascades observed in the case of carbohydrate catabolism as opposed to long regulatory cascades seen in the case of biofilm and chemotaxis pathways (Fig. 2a). CRP resides at the top of both subnetworks. CRP is the only global TF acting hierarchically over local TFs for the usage of carbohydrates, whereas CRP's activity is comparable to the activity of other global regulators in the rest of the network. Note that the concentration of its effector metabolite, cyclic adenosine monophosphate (cAMP), is at par with that of adenosine triphosphate (ATP), which acts as the energetic currency of the cell.20 This suggests that CRP not only regulates the use of these substrates for producing ATP, but also senses the energetic status of the cell to decide the execution of other cellular programs.