title: Phenotypic bistability in Escherichia coli's central carbon metabolism.
abstract: Fluctuations in intracellular molecule abundance can lead to distinct, coexisting phenotypes in isogenic populations. Although metabolism continuously adapts to unpredictable environmental changes, and although bistability was found in certain substrate-uptake pathways, central carbon metabolism is thought to operate deterministically. Here, we combine experiment and theory to demonstrate that a clonal Escherichia coli population splits into two stochastically generated phenotypic subpopulations after glucose-gluconeogenic substrate shifts. Most cells refrain from growth, entering a dormant persister state that manifests as a lag phase in the population growth curve. The subpopulation-generating mechanism resides at the metabolic core, overarches the metabolic and transcriptional networks, and only allows the growth of cells initially achieving sufficiently high gluconeogenic flux. Thus, central metabolism does not ensure the gluconeogenic growth of individual cells, but uses a population-level adaptation resulting in responsive diversification upon nutrient changes.
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kotte
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Volkmer
authors.affiliation: Molecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands.
authors.forename: Jakub L
authors.initials: JL
authors.lastname: Radzikowski
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland Molecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands m.heinemann@rug.nl.
authors.forename: Matthias
authors.initials: M
authors.lastname: Heinemann
mesh_terms: D000222:Adaptation, Physiological; D000900:Anti-Bacterial Agents; D002244:Carbon / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005947:Glucose / Q000378:metabolism*; D010641:Phenotype; D013312:Stress, Physiological
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D002244:Carbon; D005947:Glucose
keywords: bistability; flux sensing; metabolism; noise; persisters