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dc.contributor.authorRay, J. Christian J.
dc.contributor.authorWickersheim, Michelle L.
dc.contributor.authorJalihal, Ameya P.
dc.contributor.authorAdeshina, Yusuf O.
dc.contributor.authorCooper, Tim F.
dc.contributor.authorBalázsi, Gábor
dc.date.accessioned2017-11-30T21:38:22Z
dc.date.available2017-11-30T21:38:22Z
dc.date.issued2016-03-24
dc.identifier.citationRay JCJ, Wickersheim ML, Jalihal AP, Adeshina YO, Cooper TF, Balázsi G (2016) Cellular Growth Arrest and Persistence from Enzyme Saturation. PLoS Comput Biol 12(3): e1004825. https://doi.org/10.1371/journal.pcbi.1004825en_US
dc.identifier.urihttp://hdl.handle.net/1808/25531
dc.description.abstractMetabolic efficiency depends on the balance between supply and demand of metabolites, which is sensitive to environmental and physiological fluctuations, or noise, causing shortages or surpluses in the metabolic pipeline. How cells can reliably optimize biomass production in the presence of metabolic fluctuations is a fundamental question that has not been fully answered. Here we use mathematical models to predict that enzyme saturation creates distinct regimes of cellular growth, including a phase of growth arrest resulting from toxicity of the metabolic process. Noise can drive entry of single cells into growth arrest while a fast-growing majority sustains the population. We confirmed these predictions by measuring the growth dynamics of Escherichia coli utilizing lactose as a sole carbon source. The predicted heterogeneous growth emerged at high lactose concentrations, and was associated with cell death and production of antibiotic-tolerant persister cells. These results suggest how metabolic networks may balance costs and benefits, with important implications for drug tolerance.en_US
dc.publisherPublic Library of Scienceen_US
dc.rights© 2016 Ray et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleCellular Growth Arrest and Persistence from Enzyme Saturationen_US
dc.typeArticleen_US
kusw.kudepartmentMolecular Biosciencesen_US
dc.identifier.doi10.1371/journal.pcbi.1004825en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.rights.accessrightsopenAccessen_US


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© 2016 Ray et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as: © 2016 Ray et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.