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PreprintCited by 107Gene Regulatory Network AnalysisBacterial Genetics and BiotechnologyMicrobial Metabolic Engineering and Bioproduction

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Stochasticity of cellular growth: sources, propagation and consequences

Open access
Thomas, Philipp, Terradot, Guillaume, Danos, Vincent, Weiße, Andrea Y.·2018·Nature Communications
DOI 10.1101/267658PMC PMC6207721

Preprint — published as 10.1038/s41467-018-06912-9 · Paper page

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Abstract

Cellular growth impacts a range of phenotypic responses. Identifying the sources of fluctuations in growth and how they propagate across the cellular machinery can unravel mechanisms that underpin cell decisions. We present a stochastic cell model linking gene expression, metabolism and replication to predict growth dynamics in single bacterial cells. In addition to several population-averaged data, the model quantitatively recovers how growth fluctuations in single cells change across nutrient conditions. We develop a framework to analyse stochastic chemical reactions coupled with cell divisions and use it to identify sources of growth heterogeneity. By visualising cross-correlations we then determine how such initial fluctuations propagate to growth rate and affect other cell processes. We further study antibiotic responses and find that complex drug-nutrient interactions can both enhance and suppress heterogeneity. Our results provide a predictive framework to integrate single-cell and bulk data and draw testable predictions with implications for antibiotic tolerance, evolutionary biology and synthetic biology.

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Metadata

Authors
Thomas, P., Terradot, G., Danos, V., & Weiße, A. Y.
Affiliations
  • Imperial College London (GB)
  • University of Edinburgh (GB)
  • National Institute for Health and Care Research (GB)
Corresponding author
Thomas, Philipp
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2018-02-18
Volume
9
Issue
1
Pages
4528-4528
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/267658
PMC
PMC6207721
OpenAlex
W2898222917
Cited by
107
References
1
Citations by year
2026: 5 · 2025: 17 · 2024: 13 · 2023: 11 · 2022: 18 · 2021: 15 · 2020: 17 · 2019: 9 · 2018: 2
FWCI
3.82
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
  • HAL (submittedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
  • National Institute for Health Research Health Protection Research Unit
  • National Institute for Health and Care Research
  • Royal Commission for the Exhibition of 1851
  • Imperial College London (EP/N014529/1)
  • Public Health England
  • Engineering and Physical Sciences Research Council (EP/N014529/1, EP/N014529/)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
Keywords
bacterial growth, growth heterogeneity, randomness, gene expression, bacterial metabolism, DNA replication, stochastic chemical reactions, cell division, parameter estimation, sensitivity analysis, drug-nutrient interactions, antibiotics, antibiotic tolerance
MeSH terms
Bacteria, Cell Division, Models, Biological, Stochastic Processes, Gene Expression, Cell Enlargement

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