Induction kinetics of a conditional pH stress response system in Escherichia coli

TL;DR

This study quantitatively characterizes the induction kinetics of the Cad pH stress response system in E. coli, revealing a transient response driven by negative feedback from external cadaverine and providing insights into its regulatory mechanism.

Contribution

It introduces a quantitative model of the Cad system's transient response, elucidating the role of negative feedback and constraining the signal transduction mechanism.

Findings

The Cad system exhibits a transient response even under persistent inducing conditions.

Negative feedback by external cadaverine explains the transient behavior.

The model constrains the possible mechanisms of CadC-mediated signal transduction.

Abstract

The analysis of stress response systems in microorganisms can reveal molecular strategies for regulatory control and adaptation. Here, we focus on the Cad module, a subsystem of E. coli's response to acidic stress, which is conditionally activated at low pH only when lysine is available. When expressed, the Cad system counteracts the elevated H+ concentration by converting lysine to cadaverine under the consumption of H+, and exporting cadaverine in exchange for external lysine. Surprisingly, the cad operon displays a transient response, even when the conditions for its induction persist. To quantitatively characterize the regulation of the Cad module, we have experimentally recorded and theoretically modeled the dynamics of important system variables. We establish a quantitative model that adequately describes and predicts the transient expression behavior for various initial conditions. Our quantitative analysis of the Cad system supports a negative feedback by external cadaverine as the origin of the transient response. Furthermore, the analysis puts causal constraints on the precise mechanism of signal transduction via the regulatory protein CadC.