Figure 1. Temporal dynamics of two-component systems.

(A) PhoQ-PhoP is a canonical two-component system that is activated by low extracellular Mg⁺⁺, changes in pH, and certain antimicrobial peptides. Upon sensing a stimulus, PhoQ is predominantly in the kinase state, driving PhoP phosphorylation and the increased expression of PhoP target genes, including phoPQ and mgrB (left). As MgrB accumulates, it helps drive a switch of PhoQ from the kinase to the phosphatase state. Eventually PhoQ is predominantly a phosphatase, limiting expression of PhoP-dependent genes (right). (B) This negative feedback loop mediated by MgrB likely accounts for the partial adaptation in pathway output. (C) Sporulation in B. subtilis is initiated by a four step phosphorelay. KinA (shown) or KinB/C/D/E first autophosphorylate; a phosphoryl group is then transferred to the response regulator Spo0F, then to the histidine phosphotransferase Spo0B, and finally to Spo0A (black arrows). Phosphorylated Spo0A directly promotes expression of itself and Spo0F (solid grey arrows), and indirectly promotes the production of KinA (dashed grey arrow). Phosphorylated Spo0A also indirectly drives dephosphorylation of itself and Spo0F (dashed grey lines). (D) Somehow these feedback loops produce pulses of phosphorylated Spo0A in sporulation-inducing conditions. Each pulse exhibits higher levels until a threshold level is reached to initiate sporulation.