Conservation of the transcriptional cross-regulatory network in bacteria To what extent can our observations on E. coli transcriptional network be generalised to other bacteria? To address this question, we have compiled orthologs of E. coli TFs across 216 non-redundant bacterial genomes (using the approach described in Ref. 67) and analysed their conservation. As a general observation, global regulators (and negatively autoregulated TFs) of E. coli tend to be more conserved than more specialised regulators (see Fig. 4). In spite of this observation, previous studies indicated that even the TFs found at the top of regulatory hierarchies vary across bacterial phyla.67–69 Intriguingly, orthologs of CsgD and FlhCD are found in less than 25 genomes, whereas orthologs for OmpR and FliA are found in more than 75 genomes. More precisely, FliA appears to be conserved in many organisms lacking FlhCD orthologs, although FlhCD is involved in the transcriptional regulation of FliA in E. coli. Tentatively, in these organisms, a different TF might regulate FliA. Alternatively, FliA alone might control the transcription of genes required in the final stages of motility and chemotaxis, or FliA might be directing the transcription of genes for unrelated functions in these bacteria. This set of regulatory components and the corresponding network structure are likely to be conserved in a relatively small group of bacteria (less than 25 bacteria closely related to E. coli). However, the general network organisation (long regulatory cascades versus multiple FFLs, and endogenous versus exogenous sensing) apparently constitute a common theme for the regulation of physiological and developmental processes in bacteria.