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1.
Mol Syst Biol ; 17(7): e9832, 2021 07.
Article in English | MEDLINE | ID: mdl-34286912

ABSTRACT

Genetically identical individuals in bacterial populations can display significant phenotypic variability. This variability can be functional, for example by allowing a fraction of stress prepared cells to survive an otherwise lethal stress. The optimal fraction of stress prepared cells depends on environmental conditions. However, how bacterial populations modulate their level of phenotypic variability remains unclear. Here we show that the alternative sigma factor σV circuit in Bacillus subtilis generates functional phenotypic variability that can be tuned by stress level, environmental history and genetic perturbations. Using single-cell time-lapse microscopy and microfluidics, we find the fraction of cells that immediately activate σV under lysozyme stress depends on stress level and on a transcriptional memory of previous stress. Iteration between model and experiment reveals that this tunability can be explained by the autoregulatory feedback structure of the sigV operon. As predicted by the model, genetic perturbations to the operon also modulate the response variability. The conserved sigma-anti-sigma autoregulation motif is thus a simple mechanism for bacterial populations to modulate their heterogeneity based on their environment.


Subject(s)
Gene Expression Regulation, Bacterial , Sigma Factor , Bacillus subtilis/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Biological Variation, Population , Homeostasis , Humans , Operon/genetics , Sigma Factor/genetics , Sigma Factor/metabolism
2.
Nat Commun ; 9(1): 5333, 2018 12 17.
Article in English | MEDLINE | ID: mdl-30559445

ABSTRACT

Gene expression can be noisy, as can the growth of single cells. Such cell-to-cell variation has been implicated in survival strategies for bacterial populations. However, it remains unclear how single cells couple gene expression with growth to implement these strategies. Here, we show how noisy expression of a key stress-response regulator, RpoS, allows E. coli to modulate its growth dynamics to survive future adverse environments. We reveal a dynamic positive feedback loop between RpoS and growth rate that produces multi-generation RpoS pulses. We do so experimentally using single-cell, time-lapse microscopy and microfluidics and theoretically with a stochastic model. Next, we demonstrate that E. coli prepares for sudden stress by entering prolonged periods of slow growth mediated by RpoS. This dynamic phenotype is captured by the RpoS-growth feedback model. Our synthesis of noisy gene expression, growth, and survival paves the way for further exploration of functional phenotypic variability.


Subject(s)
Bacterial Proteins/biosynthesis , Escherichia coli Proteins/biosynthesis , Escherichia coli/growth & development , Escherichia coli/genetics , Gene Expression Regulation, Bacterial/genetics , Sigma Factor/biosynthesis , Bacterial Proteins/genetics , Escherichia coli Proteins/genetics , Microfluidics , Sigma Factor/genetics , Time-Lapse Imaging
3.
Chemistry ; 20(23): 6853-6, 2014 Jun 02.
Article in English | MEDLINE | ID: mdl-24806100

ABSTRACT

Self-assembly of the amphiphilic π-conjugated carbenium ion ATOTA-1(+) in aqueous solution selectively leads to discrete and highly stable nanotubes or nanoribbons and nanorods, depending on the nature of the counterion (Cl(-) vs. PF6(-), respectively). The nanotubes formed by the Cl(-) salt illustrate an exceptional example of a structural well-defined (29±2 nm in outer diameter) unilamellar tubular morphology featuring π-conjugated functionality and high stability and flexibility, in aqueous solution.

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