ArticlePLoS computational biology2013
Tunable stochastic pulsing in the Escherichia coli multiple antibiotic resistance network from interlinked positive and negative feedback loops.
Article in PLoS computational biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 46 citations in OpenAlex.
- Pulsatile basal gene expression as a fitness determinant in bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cross-evaluation of E. coli's operon structures via a whole-cell model suggests alternative cellular benefits for low- versus high-expressing operons.Cell systems · 2024Article
- Analysis and design of single-cell experiments to harvest fluctuation information while rejecting measurement noise.Frontiers in cell and developmental biology · 2023Article
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- Dynamic gene expression and growth underlie cell-to-cell heterogeneity inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Dynamic Boolean modelling reveals the influence of energy supply on bacterial efflux pump expression.Journal of the Royal Society, Interface · 2022Article
- Tunable phenotypic variability through an autoregulatory alternative sigma factor circuit.Molecular systems biology · 2021Article
- A forecast for large-scale, predictive biology: Lessons from meteorology.Cell systems · 2021Review
- Characterizing Escherichia coli's transcriptional response to different styrene exposure modes reveals novel toxicity and tolerance insights.Journal of industrial microbiology & biotechnology · 2021Article
- Simultaneous cross-evaluation of heterogeneousScience (New York, N.Y.) · 2020Article
- Active degradation of MarA controls coordination of its downstream targets.PLoS computational biology · 2018Article
- Multiplexed deactivated CRISPR-Cas9 gene expression perturbations deter bacterial adaptation by inducing negative epistasis.Communications biology · 2018Article
- CRISPR Gene Perturbations Provide Insights for Improving Bacterial Biofuel Tolerance.Frontiers in bioengineering and biotechnology · 2018Article
- Customized Regulation of Diverse Stress Response Genes by the Multiple Antibiotic Resistance Activator MarA.PLoS computational biology · 2017Article
- Deconstructing a multiple antibiotic resistance regulation through the quantification of its input function.NPJ systems biology and applications · 2017Article
- Effects of cell cycle noise on excitable gene circuits.Physical biology · 2016Article
- Antagonistic autoregulation speeds up a homogeneous response in Escherichia coli.Scientific reports · 2016Article
- Efflux Pump Control Alters Synthetic Gene Circuit Function.ACS synthetic biology · 2016Article
- Performing selections under dynamic conditions for synthetic biology applications.Integrative biology : quantitative biosciences from nano to macro · 2016Article
- Stochastic expression of a multiple antibiotic resistance activator confers transient resistance in single cells.Scientific reports · 2016Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cells live in uncertain, dynamic environments and have many mechanisms for sensing and responding to changes in their surroundings. However, sudden fluctuations in the environment can be catastrophic to a population if it relies solely on sensory responses, which have a delay associated with them. Cells can reconcile these effects by using a tunable stochastic response, where in the absence of a stressor they create phenotypic diversity within an isogenic population, but use a deterministic response when stressors are sensed. Here, we develop a stochastic model of the multiple antibiotic resistance network of Escherichia coli and show that it can produce tunable stochastic pulses in the activator MarA. In particular, we show that a combination of interlinked positive and negative feedback loops plays an important role in setting the dynamics of the stochastic pulses. Negative feedback produces a pulsatile response that is tunable, while positive feedback serves to amplify the effect. Our simulations show that the uninduced native network is in a parameter regime that is of low cost to the cell (taxing resistance mechanisms are expressed infrequently) and also elevated noise strength (phenotypic variability is high). The stochastic pulsing can be tuned by MarA induction such that variability is decreased once stresses are sensed, avoiding the detrimental effects of noise when an optimal MarA concentration is needed. We further show that variability in the expression of MarA can act as a bet hedging mechanism, allowing for survival in time-varying stress environments, however this effect is tunable to allow for a fully induced, deterministic response in the presence of a stressor.
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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.