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Role of Autoregulation and Relative Synthesis of Operon Partners in Alternative Sigma Factor Networks.

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 ?B 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 ?B, its anti-sigma factor RsbW and the anti-anti-sigma factor RsbV plays a critical role in shaping the network behavior by forcing the ?B 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.

SUBMITTER: Narula J

PROVIDER: S-EPMC5207722 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Role of Autoregulation and Relative Synthesis of Operon Partners in Alternative Sigma Factor Networks.

Narula Jatin J Tiwari Abhinav A Igoshin Oleg A OA

PLoS computational biology 20161215 12

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 ...[more]

PMID: 27977677

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Project description:Two small quorum sensing (QS) peptides regulate competence in S. mutans in a cell density dependent manner: XIP (sigX inducing peptide) and CSP (competence stimulating peptide). Depending on the environmental conditions isogenic S. mutans cells can split into a competent and non-competent subpopulation. The origin of this population heterogeneity has not been experimentally determined and it is unknown how the two QS systems are connected. We developed a toolbox of single and dual fluorescent reporter strains and systematically knocked out key genes of the competence signaling cascade in the reporter strain backgrounds. By following signal propagation on the single cell level we discovered that the master regulator of competence, the alternative sigma factor SigX, directly controls expression of the response regulator for bacteriocin synthesis ComE. Consequently, a SigX binding motif (cin-box) was identified in the promoter region of comE. Overexpressing the genetic components involved in competence development demonstrated that ComRS represents the origin of bimodality and determines the modality of the downstream regulators SigX and ComE. Moreover these analysis showed that there is no direct regulatory link between the two QS signaling cascades. Competence is induced through a hierarchical XIP signaling cascade, which has no regulatory input from the CSP cascade. CSP exclusively regulates bacteriocin synthesis. We suggest renaming it mutacin inducing peptide (MIP). Finally, using phosphomimetic comE mutants we show that unimodal bacteriocin production is controlled posttranslationally, thus solving the puzzling observation that in complex media competence is observed in a subpopulation only, while at the same time all cells produce bacteriocins. The control of both bacteriocin synthesis and competence through the alternative sigma-factor SigX suggests that S. mutans increases its genetic repertoire via QS controlled predation on neighboring species in its natural habitat.

Dataset Information

Role of Autoregulation and Relative Synthesis of Operon Partners in Alternative Sigma Factor Networks.

Publications

Role of Autoregulation and Relative Synthesis of Operon Partners in Alternative Sigma Factor Networks.

Similar Datasets

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