The interplay between metabolic stochasticity and cAMP-CRP regulation in single E. coli cells.

Wehrens, Martijn; Krah, Laurens H J; Towbin, Benjamin D; Hermsen, Rutger; Tans, Sander J (2023). The interplay between metabolic stochasticity and cAMP-CRP regulation in single E. coli cells. Cell reports, 42(10), p. 113284. Cell Press 10.1016/j.celrep.2023.113284

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The inherent stochasticity of metabolism raises a critical question for understanding homeostasis: are cellular processes regulated in response to internal fluctuations? Here, we show that, in E. coli cells under constant external conditions, catabolic enzyme expression continuously responds to metabolic fluctuations. The underlying regulatory feedback is enabled by the cyclic AMP (cAMP) and cAMP receptor protein (CRP) system, which controls catabolic enzyme expression based on metabolite concentrations. Using single-cell microscopy, genetic constructs in which this feedback is disabled, and mathematical modeling, we show how fluctuations circulate through the metabolic and genetic network at sub-cell-cycle timescales. Modeling identifies four noise propagation modes, including one specific to CRP regulation. Together, these modes correctly predict noise circulation at perturbed cAMP levels. The cAMP-CRP system may thus have evolved to control internal metabolic fluctuations in addition to external growth conditions. We conjecture that second messengers may more broadly function to achieve cellular homeostasis.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Towbin, Benjamin Daniel

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

2211-1247

Publisher:

Cell Press

Language:

English

Submitter:

Pubmed Import

Date Deposited:

23 Oct 2023 15:21

Last Modified:

04 Nov 2023 00:16

Publisher DOI:

10.1016/j.celrep.2023.113284

PubMed ID:

37864793

Uncontrolled Keywords:

CP: Cell biology CP: Microbiology CRP Escherichia coli cAMP-CRP gene expression heterogeneity noise regulation single cell stochasticity time lapse microscopy

URI:

https://boris.unibe.ch/id/eprint/187352

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