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.
Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O.Box 553, 33101 Tampere, Finland.
Anisha
A
Viswanathan
Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O.Box 553, 33101 Tampere, Finland.
Olga
O
Anufrieva
Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O.Box 553, 33101 Tampere, Finland.
Adrien
A
Sala
Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O.Box 553, 33101 Tampere, Finland; Institute for Systems Biology, 1441N 34th Street, Seattle, WA, 98103-8904, USA.
Olli
O
Yli-Harja
Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O.Box 553, 33101 Tampere, Finland. Electronic address: meenakshisundaram.kandhavelu@tut.fi.
Meenakshisundaram
M
Kandhavelu
D004734:Energy Metabolism; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005947:Glucose / Q000378:metabolism; D007763:Lac Operon; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013312:Stress, Physiological; D013831:Thiamine / Q000378:metabolism; D014158:Transcription, Genetic
D010710:Phosphates; D008025:Ligases; C028812:guanosine 3',5'-polyphosphate synthetases; D005947:Glucose; D013831:Thiamine
Cell phase; Nutrient stress; Signal processing; Single-cell analysis; mRNA variation