title: Phenotypic heterogeneity driven by nutrient limitation promotes growth in fluctuating environments.
abstract: Most microorganisms live in environments where nutrients are limited and fluctuate over time. Cells respond to nutrient fluctuations by sensing and adapting their physiological state. Recent studies suggest phenotypic heterogeneity(1) in isogenic populations as an alternative strategy in fluctuating environments, where a subpopulation of cells express a function that allows growth under conditions that might arise in the future(2-9). It is unknown how environmental factors such as nutrient limitation shape phenotypic heterogeneity in metabolism and whether this allows cells to respond to nutrient fluctuations. Here, we show that substrate limitation increases phenotypic heterogeneity in metabolism, and this heterogeneity allows cells to cope with substrate fluctuations. We subjected the N2-fixing bacterium Klebsiella oxytoca to different levels of substrate limitation and substrate shifts, and obtained time-resolved single-cell measurements of metabolic activities using nanometre-scale secondary ion mass spectrometry (NanoSIMS). We found that the level of NH4(+) limitation shapes phenotypic heterogeneity in N2 fixation. In turn, the N2 fixation rate of single cells during NH4(+) limitation correlates positively with their growth rate after a shift to NH4(+) depletion, experimentally demonstrating the benefit of heterogeneity. The results indicate that phenotypic heterogeneity is a general solution to two important ecological challenges-nutrient limitation and fluctuations-that many microorganisms face.
authors: Department of Environmental Systems Science, ETH Zurich, Swiss Federal Institute of Technology, Universitätsstrasse 16, 8092 Zurich, Switzerland.|Department of Environmental Microbiology, Eawag, Swiss Federal Institute of Aquatic Science and Technology, Überlandstrasse 133, 8600 Dübendorf, Switzerland.
authors: Frank
authors: F
authors: Schreiber
authors: Department of Biogeochemistry, Max Planck Institute for Marine Microbiology, Celsiusstrasse 1, 28359 Bremen, Germany.
authors: Sten
authors: S
authors: Littmann
authors: Department of Biogeochemistry, Max Planck Institute for Marine Microbiology, Celsiusstrasse 1, 28359 Bremen, Germany.
authors: Gaute
authors: G
authors: Lavik
authors: Laboratory for Biological Geochemistry, School of Architecture, Civil and Environmental Engineering (ENAC), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors: Stéphane
authors: S
authors: Escrig
authors: Laboratory for Biological Geochemistry, School of Architecture, Civil and Environmental Engineering (ENAC), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.|Center for Advanced Surface Analysis, Institute of Earth Sciences, University of Lausanne, Lausanne, Switzerland.
authors: Anders
authors: A
authors: Meibom
authors: Department of Biogeochemistry, Max Planck Institute for Marine Microbiology, Celsiusstrasse 1, 28359 Bremen, Germany.
authors: Marcel M M
authors: MM
authors: Kuypers
authors: Department of Environmental Systems Science, ETH Zurich, Swiss Federal Institute of Technology, Universitätsstrasse 16, 8092 Zurich, Switzerland.|Department of Environmental Microbiology, Eawag, Swiss Federal Institute of Aquatic Science and Technology, Überlandstrasse 133, 8600 Dübendorf, Switzerland.
authors: Martin
authors: M
authors: Ackermann
mesh_terms: D000222:Adaptation, Physiological; D064751:Ammonium Compounds / Q000378:metabolism; D018407:Bacterial Physiological Phenomena; D059647:Gene-Environment Interaction; D018740:Genetic Heterogeneity; D041121:Klebsiella oxytoca / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D013058:Mass Spectrometry; D008954:Models, Biological; D009586:Nitrogen Fixation; D010641:Phenotype; D059010:Single-Cell Analysis
chemical_list: D064751:Ammonium Compounds