Adaptable Functionality of Transcriptional Feedback in Bacterial Two-Component Systems
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.