Proposed model for VieB inhibition. Stimulation of the VieSA TCS by binding of external signal (stars) to VieS results in autophosphorylation and phosphotransfer to and activation of VieA. We propose that VieA activation results in the amplification of the vieSAB operon and up-regulation of virulence genes. We hypothesize that this up-regulation of vieA, leads to decreased intracellular levels of c-di-GMP and enhanced expression of virulence genes (A). Over time, or at high levels of transcription of the vieSAB operon, VieB accumulates. This pool of VieB is able to tightly bind, noncompetitively, to VieS. We hypothesize that this binding disrupts autophosphorylation and the transfer of phosphate between the HK and REC domains of VieS, down-modulating the phosphorelay. This lack of phosphotransfer to VieA results in down regulation of vieSAB and virulence genes (B). ‘X’ denotes the inhibitory action of VieB. Black arrows correspond to active phosphotransfer while grey arrows denote incompletion of transfer.