Helicobacter pylori Transcriptional Network

The human gastric pathogen Helicobacter pylori appears to enroll only 17 transcriptional regulators to transduce environmental signals into coordinated output expression of the genome. We show that the low number of transcriptional regulators, together with the large body of molecular tools, set H. pylori as appealing model organism to characterize transcriptional network structures involved in virulence regulation and host-pathogen interactions. In particular we provide evidence that the regulators are wired in a shallow transcriptional regulatory network (TRN), which orchestrates the key physiological responses needed to colonize the gastric niche: heat and stress response, motility and chemotaxis, acid acclimation and metal ion homeostasis. Interestingly, long regulatory cascades are absent, and rather than having a plethora of specialized regulators, the TRN of H. pylori appears to transduce separate environmental inputs by using different combinations of a small set of regulators. It is not tailored to adapt to many environmental stimuli, and apparently not flexible to react to metabolic signals encountered outside of the gastric niche. On the other hand, the predominance of negative regulatory interactions suggests that this architecture of the TRN evolved to quickly respond to changing conditions in the gastric niche in order to maintain homeostasis. Metal-responsive regulators such as NikR and Fur appear to have a very important role in this TRN, forming a central regulatory hub, with regulatory interaction feeding into all other sub-network circuits.