ppGpp and DksA likely regulate the activity of the extracytoplasmic stress factor ς^E in Escherichia coli by both direct and indirect mechanisms

One of the major signalling pathways responsible for intercompartmental communication between the cell envelope and cytoplasm in Escherichia coli is mediated by the alternative sigma factor, ς^E. ς^E has been studied primarily for its role in response to the misfolding of outer membrane porins. This response is essentially reactionary; cells are stressed, porin folding is disrupted, and the response is activated. ς^E can also be activated following starvation for a variety of nutrients by the alarmone ppGpp. This response is proactive, as ς^E is activated in the absence of any obvious damage to the cell envelope sensed by the stress signalling pathway. Here we examine the mechanism of regulation of ς^E by ppGpp. ppGpp has been proposed to activate at least two alternative sigma factors, ς^N and ς^S, indirectly by altering the competition for core RNA polymerase between the alternative sigma factors and the housekeeping sigma factor, ς⁷⁰. In vivo experiments with ς^E are consistent with this model. However, ppGpp and its cofactor DksA can also activate transcription by Eς^Ein vitro, suggesting that the effects of ppGpp on ς^E activity are both direct and indirect.