Abstract
Despite the central role of alternative sigma factors in bacterial stress response and virulence their regulation remains incompletely understood. Here we investigate one of the best-studied examples of alternative sigma factors: the σB network that controls the general stress response of Bacillus subtilis to uncover widely relevant general design principles that describe the structure-function relationship of alternative sigma factor regulatory networks. We show that the relative stoichiometry of the synthesis rates of σB, its anti-sigma factor RsbW and the anti-anti-sigma factor RsbV plays a critical role in shaping the network behavior by forcing the σB network to function as an ultrasensitive negative feedback loop. We further demonstrate how this negative feedback regulation insulates alternative sigma factor activity from competition with the housekeeping sigma factor for RNA polymerase and allows multiple stress sigma factors to function simultaneously with little competitive interference.
Highlights
Bacteria survive in stressful environmental conditions by inducing dramatic changes in their gene expression patterns [1,2]
Here we study one of the longest serving model systems of bacterial stress response: the σB pathway of Bacillus subtilis
Using mathematical modeling we identify the core structural design feature of the network that are responsible for its pulsatile response
Summary
Bacteria survive in stressful environmental conditions by inducing dramatic changes in their gene expression patterns [1,2]. To ensure that these σ-factors are only active under specific environmental conditions, bacteria have evolved regulatory systems to control their production, activity and availability [3,4]. These regulatory networks can be highly complex but frequently share features such as anti-σfactors, partner switching mechanisms and proteolytic activation [4]. The complexity of these networks has impeded a clear mechanistic understanding of the resulting dynamical properties. We focus on one of the best studied examples of alternative σ-factors, the general stress-response regulating σB in Bacillus subtilis [5] to understand how the structure of the σ-factor regulatory networks is related to their functional response
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