Figure 2. Stochastic pulsing mediated by interlinked positive and negative feedback and tuned by inducer levels.

(A) Schematic representation of the four variants of the marRAB network studied. The Wildtype case has binding sites for MarA and MarR₂, Only Positive eliminates both binding sites for MarR₂, Only Negative eliminates the MarA binding site, and No Feedback has constant, constitutive expression. (B) Stochastic simulations of the four network variants. Noise amplification is observed in the Only Positive variant, transcriptional bursting appears in the Only Negative case, and both characteristics are combined to create high-amplitude stochastic pulsing in the Wildtype network. (C) Coefficient of variation (CV, std/mean) of MarA as a function of salicylate concentration. Constant noise is observed for the variants that do not respond to salicylate (Only Positive and No Feedback). The salicylate-responsive variants (Wildtype and Only Negative) show a decrease in CV upon induction. (D) Noise strength (var/mean) of MarA as a function of salicylate. Error bars in (C) and (D) show standard deviation across 100 replicates.