Model of the BetR-mediated lifestyle switch in Serratia. In response to an unknown periplasmic signal, likely extracellular in origin, Reg1 interacts with the periplasmic sensing domain of Reg2, causing autophosphorylation and dimerization of the histidine kinase domains (phosphotransfer indicated by dashed arrows). This causes phosphorylation of the receiver domain of BetR, either directly from the Reg2 phosphoacceptor domain or via the Reg2 receiver domain and an unknown histidine-containing phosphotransfer protein (Hpt), leading to BetR dimerization and interaction of its DNA-binding domain with DNA, altering transcription of many target genes. The transcriptional response causes a concerted lifestyle switch from an adhesive, passive, and potentially resilient mode to an aggressive, motile, and likely pioneering mode via transcriptional regulation of multiple operons and post-translational regulation of T6SS_i3v1 activity. Protein domains are colored as in Figure 2; IM, inner membrane; OM, outer membrane.
