Single-cell dynamics reveals sustained growth during diauxic shifts

PLoS One. 2013 Apr 30;8(4):e61686. doi: 10.1371/journal.pone.0061686. Print 2013.

Abstract

Stochasticity in gene regulation has been characterized extensively, but how it affects cellular growth and fitness is less clear. We study the growth of E. coli cells as they shift from glucose to lactose metabolism, which is characterized by an obligatory growth arrest in bulk experiments that is termed the lag phase. Here, we follow the growth dynamics of individual cells at minute-resolution using a single-cell assay in a microfluidic device during this shift, while also monitoring lac expression. Mirroring the bulk results, the majority of cells displays a growth arrest upon glucose exhaustion, and resume when triggered by stochastic lac expression events. However, a significant fraction of cells maintains a high rate of elongation and displays no detectable growth lag during the shift. This ability to suppress the growth lag should provide important selective advantages when nutrients are scarce. Trajectories of individual cells display a highly non-linear relation between lac expression and growth, with only a fraction of fully induced levels being sufficient for achieving near maximal growth. A stochastic molecular model together with measured dependencies between nutrient concentration, lac expression level, and growth accurately reproduces the observed switching distributions. The results show that a growth arrest is not obligatory in the classic diauxic shift, and underscore that regulatory stochasticity ought to be considered in terms of its impact on growth and survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Escherichia coli / genetics*
  • Escherichia coli / growth & development*
  • Escherichia coli / metabolism
  • Gene Expression Regulation, Bacterial*
  • Glucose / metabolism*
  • Lac Operon
  • Lactose / metabolism*
  • Models, Biological
  • Single-Cell Analysis
  • Stochastic Processes

Substances

  • Glucose
  • Lactose

Grants and funding

This work is part of the research program of the Foundation for Fundamental Research on Matter (FOM), which is part of the Netherlands Organization for Scientific Research (NWO). S.B. was supported by Netherlands Institute for Systems Biology (NISB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.