ArticleProceedings of the National Academy of Sciences of the United States of America2012
Ultrasensitivity of the Bacillus subtilis sporulation decision.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 75 citations in OpenAlex.
- Evolutionary bioenergetics of sporulation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Analysis of Proteome Dynamics in Early-Stage Sporulation-Inhibited Variants ofInternational journal of molecular sciences · 2025Article
- Biophysical modeling reveals the transcriptional regulatory mechanism of Spo0A, the master regulator in starvingmSystems · 2025Article
- Acetylation of the histone-like protein HBsu at specific sites alters gene expression during sporulation inFrontiers in microbiology · 2025Article
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- Transcription-replication interactions reveal principles of bacterial genome regulation.Research square · 2023Article
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- Sporulation in solventogenic and acetogenic clostridia.Applied microbiology and biotechnology · 2021Review
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- Maximization of information transmission influences selection of native phosphorelay architectures.PeerJ · 2021Article
- Molecular changes associated with spontaneous phenotypic variation of Paenibacillus polymyxa, a commonly used biocontrol agent, and temperature-dependent control of variation.Scientific reports · 2020Article
- Predictive biology: modelling, understanding and harnessing microbial complexity.Nature reviews. Microbiology · 2020Review
- Artificial Sporulation Induction (ASI) byInternational journal of molecular sciences · 2020Article
- Morphological State Transition Dynamics in EGF-Induced Epithelial to Mesenchymal Transition.Journal of clinical medicine · 2019Article
- Differentiation of Vegetative Cells into Spores: a Kinetic Model Applied to Bacillus subtilis.Applied and environmental microbiology · 2019Article
- Role of metabolic spatiotemporal dynamics in regulating biofilm colony expansion.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Dynamic sporulation gene co-expression networks for Bacillus subtilis 168 and the food-borne isolate Bacillus amyloliquefaciens: a transcriptomic model.Microbial genomics · 2018Article
- Cell Death Pathway That Monitors Spore Morphogenesis.Trends in microbiology · 2017Review
- Switch-like Transitions Insulate Network Motifs to Modularize Biological Networks.Cell systems · 2016Article
- Slowdown of growth controls cellular differentiation.Molecular systems biology · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Starving Bacillus subtilis cells execute a gene expression program resulting in the formation of stress-resistant spores. Sporulation master regulator, Spo0A, is activated by a phosphorelay and controls the expression of a multitude of genes, including the forespore-specific sigma factor σ(F) and the mother cell-specific sigma factor σ(E). Identification of the system-level mechanism of the sporulation decision is hindered by a lack of direct control over Spo0A activity. This limitation can be overcome by using a synthetic system in which Spo0A activation is controlled by inducing expression of phosphorelay kinase KinA. This induction results in a switch-like increase in the number of sporulating cells at a threshold of KinA. Using a combination of mathematical modeling and single-cell microscopy, we investigate the origin and physiological significance of this ultrasensitive threshold. The results indicate that the phosphorelay is unable to achieve a sufficiently fast and ultrasensitive response via its positive feedback architecture, suggesting that the sporulation decision is made downstream. In contrast, activation of σ(F) in the forespore and of σ(E) in the mother cell compartments occurs via a cascade of coherent feed-forward loops, and thereby can produce fast and ultrasensitive responses as a result of KinA induction. Unlike σ(F) activation, σ(E) activation in the mother cell compartment only occurs above the KinA threshold, resulting in completion of sporulation. Thus, ultrasensitive σ(E) activation explains the KinA threshold for sporulation induction. We therefore infer that under uncertain conditions, cells initiate sporulation but postpone making the sporulation decision to average stochastic fluctuations and to achieve a robust population response.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.