Dynamics of an Interactive Network Composed of a Bacterial Two-Component System, a Transporter and K+ as Mediator

KdpD and KdpE form a histidine kinase/response regulator system that senses K + limitation and induces the kdpFABC operon, which encodes a high-affinity K + uptake complex. To define the primary stimulus perceived by KdpD we focused in this study on the dynamics of the Kdp response. Escherichia coli cells were subjected to severe K + limitation, and all relevant parameters of the Kdp response, i.e., levels of kdpFABC transcripts and KdpFABC proteins, as well as extra- and intracellular K + concentrations, were quantitatively analysed over time (0 to 180 min). Unexpectedly, induction of kdpFABC was found to follow a non-monotonic time-course. To interpret this unusual behaviour, a mathematical model that adequately captures the dynamics of the Kdp system was established and used for simulations. We found a strong correlation between KdpD/KdpE activation and the intracellular K + concentration, which is influenced by the uptake of K + via the KdpFABC complex. Based on these results a model is proposed in which KdpD/KdpE phosphorylation is inversely correlated with the intracellular K + concentration. To corroborate this hypothesis an isogenic mutant that produces a defective KdpFABC complex, and the trans -complemented mutant that expresses the KtrAB high-affinity K + uptake system of Vibrio alginolyticus were quantitatively analysed. Experimental data and simulations for the mutants consistently support the tight correlation between KdpD/KdpE activation and the intracellular K + concentration. This study presents a striking example of the non-intuitive dynamics of a functional unit comprising signalling proteins and a transporter with K + as mediator.