Abstract
The stringent response to nutrient deprivation is a stress response found throughout the bacterial domain of life. Although first described in proteobacteria for matching ribosome synthesis to the cell's translation status and for preventing formation of defective ribosomal particles, the response is actually much broader, regulating many hundreds of genes-some positively, some negatively. Utilization of the signaling molecules ppGpp and pppGpp for this purpose is ubiquitous in bacterial evolution, although the mechanisms employed vary. In proteobacteria, the signaling molecules typically bind to two sites on RNA polymerase, one at the interface of the β' and ω subunits and one at the interface of the β' secondary channel and the transcription factor DksA. The β' secondary channel is targeted by other transcription regulators as well. Although studies on the transcriptional outputs of the stringent response date back at least 50 years, the mechanisms responsible are only now coming into focus.