Adaptable Functionality of Transcriptional Feedback in Bacterial Two-Component Systems
Figure 2
Conditions for negative feedback and overshoot in a two-component system model.
A. Monte Carlo parameter sampling shows that both positive and negative feedback are attainable with the model. Overshoot kinetics only occur when the feedback sign is negative. The y axis is fraction of contribution of JE, the flux of exogenous response regulator phosphorylation, relative to the total phosphorylation flux that also includes JS, the flux of sensor histidine kinase-mediated phosphorylation. Negative feedback cases all have a proportion of exogenous flux above ∼0.001 (i.e. 0.1%). “Overshoot” cases denote a peak phosphorylated response regulator dimer (RRP)2 concentration greater than 50% above the activated steady state. Open-loop gain is calculated as response of the open-loop system to perturbation of an exogenous regulator (R0) at the activated steady state (kph = 0.1). B. Comparison of simulated overshoot kinetics and experimental measurement of mgtA-bound RRP (phospho-PhoP) in Salmonella (adapted from 11). The “No Feedback” case takes a constitutive expression level equal to the activated steady state of the “With Feedback” case in the simulations. Simulations used the reference parameter set in Table S1.