Abstract

Frequent changes in nutrient availability often result in repeated cycles of bacterial growth and dormancy. The timing of growth resumption can differ among isogenic cells and delayed growth resumption can lead to antibiotic tolerant persisters. Here we describe a correlation between the timing of entry into stationary phase and resuming growth in the next period of cell proliferation. E. coli cells can follow a last in first out rule: the last ones to shut down their metabolism in the beginning of stationary phase are the first to recover in response to nutrients. This memory effect can last for several days in stationary phase and is not influenced by environmental changes. We observe that the speed and heterogeneity of growth resumption depends on the carbon source. A good carbon source (glucose) can promote rapid growth resumption even at low concentrations, and is seen to act more like a signal than a growth substrate. Heterogeneous growth resumption can protect the population from adverse effect of stress, investigated here using heat-shock, because the stress-resilient dormant cells are always present.

Highlights

  • Frequent changes in nutrient availability often result in repeated cycles of bacterial growth and dormancy

  • E. coli cells, carrying two plasmids encoding for fluorescent proteins GFP and Crimson, are grown into stationary phase with Crimson expression induced

  • Some cells can significantly delay their growth resumption in a growth supporting environment, leading to the co-existance of growing and dormant cells[2,4]. Dormant cells in these populations can be identified as persisters: cells that are tolerant to antibiotics and can reinitiate growth when antibiotics are removed[5]

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Summary

Introduction

Frequent changes in nutrient availability often result in repeated cycles of bacterial growth and dormancy. E. coli cells can follow a last in first out rule: the last ones to shut down their metabolism in the beginning of stationary phase are the first to recover in response to nutrients. Wt E. coli strains display heterogeneity in growth resumption timing and many cells display a long lag phase[2,3,4]. This suggests that, despite favorable conditions, delaying growth resumption could be advantageous. Stationary phase cells are often considered to be similar to each other and no markers have been described that would predict the timing of regrowth of individual cells. A correspondence between the status of each cell at the beginning of stationary phase and the timing of growth resumption is maintained over several days indicating the existence of long-term ‘memory’ in E. coli cultures

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