Phase-dependent dynamics of the lac promoter under nutrient stress

To survive, a bacterial population must sense nutrient availability and adjust its growth phase accordingly. Few studies have quantitatively analyzed the single-cell behavior of stress and growth phase-related transcriptional changes in Escherichia coli. To investigate the dynamic changes in transcription during different growth phases and starvation, we analyzed the single-cell transcriptional dynamics of the E. coli lac promoter. Cells were grown under different starvation conditions, including glucose, magnesium, phosphate and thiamine limitations, and transcription dynamics was quantified using a single RNA detection method at different phases. Differences in gene expression over conditions and phases indicate that stochasticity in transcription dynamics is directly connected to cell phase and availability of nutrients. Except for glucose, the pattern of transcription dynamics under all starvation conditions appears to be similar. Transcriptional bursts were more prominent in lag and stationary phase cells starved for energy sources. Identical behavior was observed in exponential phase cells starved for phosphate and thiamine. Noise measurements under all nutrient exhaustion conditions indicate that intrinsic noise is higher than extrinsic noise. Our results, obtained in a relA1 mutational background, which led to suboptimal production of ppGpp, suggest that the single-cell transcriptional changes we observed were largely ppGpp-independent. Taken together, we propose that, under different starvation conditions, cells are able to decrease the trend in cell-to-cell variability in transcription as a common means of adaptation.