Growth phase-dependent regulation of the extracytoplasmic stress factor, σ^E, by guanosine 3′,5′-bispyrophosphate (ppGpp)

The sigma subunit of procaryotic RNA polymerases is responsible for specific promoter recognition and transcription initiation. In addition to the major sigma factor, σ⁷⁰, in Escherichia coli, which directs most of the transcription in the cell, bacteria possess multiple, alternative sigma factors that direct RNA polymerase to distinct sets of promoters in response to environmental signals. By activating an alternative sigma factor, gene expression can be rapidly reprogrammed to meet the needs of the cell as the environment changes. Sigma factors are subject to multiple levels of regulation that control their levels and activities. The alternative sigma factor σ^E in Escherichia coli is induced in response to extracytoplasmic stress. Here we demonstrate that σ^E can also respond to signals other than extracytoplasmic stress. σ^E activity increases in a growth phase-dependent manner as a culture enters stationary phase. The signaling pathway that activates σ^E during entry into stationary phase is dependent upon the alarmone guanosine 3′,5′-bispyrophosphate (ppGpp) and is distinct from the pathway that signals extracytoplasmic stress. ppGpp is the first cytoplasmic factor shown to control σ^E activity, demonstrating that σ^E can respond to internal signals as well as signals originating in the cell envelope. ppGpp is a general signal of starvation stress and is also required for activation of the σ^S and σ⁵⁴ alternative sigma factors upon entry into stationary phase, suggesting that this is a key mechanism by which alternative sigma factors can be activated in concert to provide a coordinated response to nutritional stress.