Dynamic gene expression and growth underlie cell-to-cell heterogeneity in Escherichia coli stress response

Abstract

Cell-to-cell heterogeneity in gene expression and growth can have critical functional consequences, such as determining whether individual bacteria survive or die following stress. Although phenotypic variability is well documented, the dynamics that underlie it are often unknown. This information is important because dramatically different outcomes can arise from gradual versus rapid changes in expression and growth. Using single-cell time-lapse microscopy, we measured the temporal expression of a suite of stress response reporters in Escherichia coli, while simultaneously monitoring growth rate. In conditions without stress, we found several examples of pulsatile expression. Single-cell growth rates were often anti-correlated with gene expression, with changes in growth preceding changes in expression. These expression and growth dynamics have functional consequences, which we demonstrate by measuring survival after challenging cells with the antibiotic ciprofloxacin. Our results suggest that fluctuations in gene expression and growth dynamics in stress response networks can have direct consequences for survival.