title: The last generation of bacterial growth in limiting nutrient.
abstract: BACKGROUND
  Bacterial growth as a function of nutrients has been studied for decades, but is still not fully understood. In particular, the growth laws under dynamically changing environments have been difficult to explore, because of the rapidly changing conditions. Here, we address this challenge by means of a robotic assay and measure bacterial growth rate, promoter activity and substrate level at high temporal resolution across the entire growth curve in batch culture. As a model system, we study E. coli growing under nitrogen or carbon limitation, and explore the dynamics in the last generation of growth where nutrient levels can drop rapidly.
  
  
  RESULTS
  We find that growth stops abruptly under limiting nitrogen or carbon, but slows gradually when nutrients are not limiting. By measuring growth rate at a 3 min time resolution, and inferring the instantaneous substrate level, s, we find that the reduction in growth rate μ under nutrient limitation follows Monod's law, μ=μ0(s/(k(s)+s)). By following promoter activity of different genes we found that the abrupt stop of growth under nitrogen or carbon limitation is accompanied by a pulse-like up-regulation of the expression of genes in the relevant nutrient assimilation pathways. We further find that sharp stop of growth is conditional on the presence of regulatory proteins in the assimilation pathway.
  
  
  CONCLUSIONS
  The observed sharp stop of growth accompanied by a pulsed expression of assimilation genes allows bacteria to compensate for the drop in nutrients, suggesting a strategy used by the cells to prolong exponential growth under limiting substrate.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Bren
authors.forename: Yuval
authors.initials: Y
authors.lastname: Hart
authors.forename: Erez
authors.initials: E
authors.lastname: Dekel
authors.forename: Daniel
authors.initials: D
authors.lastname: Koster
authors.forename: Uri
authors.initials: U
authors.lastname: Alon
mesh_terms: D002244:Carbon / Q000378:metabolism*; D049109:Cell Proliferation; D004926:Escherichia coli / Q000254:growth & development*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D005974:Glutamate-Ammonia Ligase / Q000235:genetics; D008954:Models, Biological; D009584:Nitrogen / Q000378:metabolism*; D009747:Nutritional Physiological Phenomena / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D002244:Carbon; C081173:glutamine synthetase I; D005974:Glutamate-Ammonia Ligase; D009584:Nitrogen