Integrated control of bacterial growth and stress response by (p)ppGpp in Escherichia coli: A seesaw fashion.

To thrive in nature, bacteria have to reproduce efficiently under favorable conditions and persist during stress. The global strategy that integrates the growth control and stress response remains to be explored. Here, we find that a moderate induction of (p)ppGpp reduces growth rate but significantly enhances the stress tolerance of E. coli, resulting from a global resource re-allocation from ribosome synthesis to the synthesis of stress-responsive proteins. Strikingly, the activation of stress response by (p)ppGpp is still largely retained in the absence of RpoS. In addition, (p)ppGpp induction could activate the catabolism of alanine and arginine, facilitating the adaption of bacteria to nutrient downshift. Our work demonstrates that the activation of stress response by (p)ppGpp could occur in an RpoS-independent manner and (p)ppGpp enables bacteria to integrate the control of growth and stress response in a seesaw fashion, thus acting as an important global regulator of the bacterial fitness landscape.