Dataset Information

Adaptable functionality of transcriptional feedback in bacterial two-component systems.

ABSTRACT: A widespread mechanism of bacterial signaling occurs through two-component systems, comprised of a sensor histidine kinase (SHK) and a transcriptional response regulator (RR). The SHK activates RR by phosphorylation. The most common two-component system structure involves expression from a single operon, the transcription of which is activated by its own phosphorylated RR. The role of this feedback is poorly understood, but it has been associated with an overshooting kinetic response and with fast recovery of previous interrupted signaling events in different systems. Mathematical models show that overshoot is only attainable with negative feedback that also improves response time. Our models also predict that fast recovery of previous interrupted signaling depends on high accumulation of SHK and RR, which is more likely in a positive feedback regime. We use Monte Carlo sampling of the parameter space to explore the range of attainable model behaviors. The model predicts that the effective feedback sign can change from negative to positive depending on the signal level. Variations in two-component system architectures and parameters may therefore have evolved to optimize responses in different bacterial lifestyles. We propose a conceptual model where low signal conditions result in a responsive system with effectively negative feedback while high signal conditions with positive feedback favor persistence of system output.

SUBMITTER: Ray JC

PROVIDER: S-EPMC2820520 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Adaptable functionality of transcriptional feedback in bacterial two-component systems.

Ray J Christian J JC Igoshin Oleg A OA

PLoS computational biology 20100212 2

A widespread mechanism of bacterial signaling occurs through two-component systems, comprised of a sensor histidine kinase (SHK) and a transcriptional response regulator (RR). The SHK activates RR by phosphorylation. The most common two-component system structure involves expression from a single operon, the transcription of which is activated by its own phosphorylated RR. The role of this feedback is poorly understood, but it has been associated with an overshooting kinetic response and with fa ...[more]

PMID: 20168997

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Project description:The prevalent paradigm governing bacterial two-component signaling systems (TCSs) is specificity, wherein the histidine kinase (HK) of a TCS exclusively activates its cognate response regulator (RR). Cross talk, where HKs activate noncognate RRs, is considered evolutionarily disadvantageous because it can compromise adaptive responses by leaking signals. Yet cross talk is observed in several bacteria. Here, to resolve this paradox, we propose an alternative paradigm where cross talk can be advantageous. We envisioned programmed environments, wherein signals appear in predefined sequences. In such environments, cross talk that primes bacteria to upcoming signals may improve adaptive responses and confer evolutionary benefits. To test this hypothesis, we employed mathematical modeling of TCS signaling networks and stochastic evolutionary dynamics simulations. We considered the comprehensive set of bacterial phenotypes, comprising thousands of distinct cross talk patterns competing in varied signaling environments. Our simulations predicted that in programmed environments phenotypes with cross talk facilitating priming would outcompete phenotypes without cross talk. In environments where signals appear randomly, bacteria without cross talk would dominate, explaining the specificity widely seen. Additionally, a testable prediction was that the phenotypes selected in programmed environments would display one-way cross talk, ensuring priming to future signals. Interestingly, the cross talk networks we deduced from available data on TCSs of Mycobacterium tuberculosis all displayed one-way cross talk, which was consistent with our predictions. Our study thus identifies potential evolutionary underpinnings of cross talk in bacterial TCSs, suggests a reconciliation of specificity and cross talk, makes testable predictions of the nature of cross talk patterns selected, and has implications for understanding bacterial adaptation and the response to interventions. IMPORTANCE Bacteria use two-component signaling systems (TCSs) to sense and respond to environmental changes. The prevalent paradigm governing TCSs is specificity, where signal flow through TCSs is insulated; leakage to other TCSs is considered evolutionarily disadvantageous. Yet cross talk between TCSs is observed in many bacteria. Here, we present a potential resolution of this paradox. We envision programmed environments, wherein stimuli appear in predefined sequences. Cross talk that primes bacteria to upcoming stimuli could then confer evolutionary benefits. We demonstrate this benefit using mathematical modeling and evolutionary simulations. Interestingly, we found signatures of predicted cross talk patterns in Mycobacterium tuberculosis. Furthermore, specificity was selected in environments where stimuli occurred randomly, thus reconciling specificity and cross talk. Implications follow for understanding bacterial evolution and for interventions.

Dataset Information

Adaptable functionality of transcriptional feedback in bacterial two-component systems.

Publications

Adaptable functionality of transcriptional feedback in bacterial two-component systems.

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