Escherichia coli can survive stress by noisy growth modulation

Gene expression can be noisy, as can the growth of single cells. Such cell-to-cell variation has been implicated in survival strategies for bacterial populations. However, it remains unclear how single cells couple gene expression with growth to implement these strategies. Here, we show how noisy expression of a key stress-response regulator, RpoS, allows E. coli to modulate its growth dynamics to survive future adverse environments. We reveal a dynamic positive feedback loop between RpoS and growth rate that produces multi-generation RpoS pulses. We do so experimentally using single-cell, time-lapse microscopy and microfluidics and theoretically with a stochastic model. Next, we demonstrate that E. coli prepares for sudden stress by entering prolonged periods of slow growth mediated by RpoS. This dynamic phenotype is captured by the RpoS-growth feedback model. Our synthesis of noisy gene expression, growth, and survival paves the way for further exploration of functional phenotypic variability.