title: Single-cell characterization of metabolic switching in the sugar phosphotransferase system of Escherichia coli.
abstract: The utilization of several sugars in Escherichia coli is regulated by the Phosphotransferase System (PTS), in which diverse sugar utilization modules compete for phosphoryl flux from the general PTS proteins. Existing theoretical work predicts a winner-take-all outcome when this flux limits carbon uptake. To date, no experimental work has interrogated competing PTS uptake modules with single-cell resolution. Using time-lapse microscopy in perfused microchannels, we analyzed the competition between N-acetyl-glucosamine and sorbitol, as representative PTS sugars, by measuring both the expression of their utilization systems and the concomitant impact of sugar utilization on growth rates. We find two distinct regimes: hierarchical usage of the carbohydrates, and co-expression of the genes for both systems. Simulations of a mathematical model incorporating asymmetric sugar quality reproduce our metabolic phase diagram, indicating that under conditions of nonlimiting phosphate flux, co-expression is due to uncoupling of both sugar utilization systems. Our model reproduces hierarchical winner-take-all behaviour and stochastic co-expression, and predicts the switching between both strategies as a function of available phosphate flux. Hence, experiments and theory both suggest that PTS sugar utilization involves not only switching between the sugars utilized but also switching of utilization strategies to accommodate prevailing environmental conditions.
authors.affiliation: Faculty of Physics and Center for NanoScience, Ludwig-Maximilans-Universität München, Geschwister-Scholl-Platz 1, D-80539, München.
authors.forename: Sonja A
authors.initials: SA
authors.lastname: Westermayer
authors.affiliation: LOEWE-Center for Synthetic Microbiology, Computational Microbiology, Philipps-Universität Marburg, Hans-Meerwein-Straße 6, D-35032, Marburg.
authors.forename: Georg
authors.initials: G
authors.lastname: Fritz
authors.affiliation: Faculty of Physics and Center for NanoScience, Ludwig-Maximilans-Universität München, Geschwister-Scholl-Platz 1, D-80539, München.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Gutiérrez
authors.affiliation: Faculty of Physics and Center for NanoScience, Ludwig-Maximilans-Universität München, Geschwister-Scholl-Platz 1, D-80539, München.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Megerle
authors.affiliation: Faculty of Physics and Center for NanoScience, Ludwig-Maximilans-Universität München, Geschwister-Scholl-Platz 1, D-80539, München.
authors.forename: Mira P S
authors.initials: MP
authors.lastname: Weißl
authors.affiliation: Institut für Genetik, Universität zu Köln, Zülpicher Straße 47a, D-50674, Köln.
authors.forename: Karin
authors.initials: K
authors.lastname: Schnetz
authors.affiliation: Physics of Complex Biosystems, Physics Department, Technical University of Munich, James-Franck-Straße 1, D-85748, Garching.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gerland
authors.affiliation: Faculty of Physics and Center for NanoScience, Ludwig-Maximilans-Universität München, Geschwister-Scholl-Platz 1, D-80539, München.
authors.forename: Joachim O
authors.initials: JO
authors.lastname: Rädler
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D057465:Catabolite Repression / Q000502:physiology; D004926:Escherichia coli / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005947:Glucose / Q000378:metabolism; D008962:Models, Theoretical; D010728:Phosphoenolpyruvate / Q000378:metabolism; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism*; D013012:Sorbitol / Q000378:metabolism*
chemical_list: D013012:Sorbitol; D010728:Phosphoenolpyruvate; D010770:Phosphotransferases; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; D005947:Glucose; D000117:Acetylglucosamine