Transcriptional regulatory module analysis reveals that bridge proteins reconcile multiple signals in extracellular electron transfer pathways.

Shewanella oneidensis MR-1 shows remarkable respiratory versatility with a large variety of extracellular electron acceptors (termed extracellular electron transfer, EET). To utilize the various electron acceptors, the bacterium must employ complex regulatory mechanisms to elicit the relevant EET pathways. To investigate the relevant mechanisms, we integrated EET genes and related transcriptional factors (TFs) into transcriptional regulatory modules (TRMs) and showed that many bridge proteins in these modules were signal proteins, which generally contained one or more signal processing domains (eg, GGDEF, EAL, PAS, etc.). Since Shewanella has to respond to diverse environmental conditions despite encoding few EET-relevant TFs, the overabundant signal proteins involved in the TRMs can help decipher the mechanism by which these microbes elicit a wide range of condition-specific responses. By combining proteomic data and protein bioinformatic analysis, we demonstrated that diverse signal proteins reconciled the different EET pathways, and we discussed the functional roles of signal proteins involved in the well-known MtrCAB pathway. Additionally, we showed that the signal proteins SO_2145 and SO_1417 played central roles in triggering EET pathways in anaerobic environments. Taken together, our results suggest that signal proteins have a profound impact on the transcriptional regulation of EET genes and thus have potential applications in microbial fuel cells.