Fig. 8: Schematic illustration of the role of (p)ppGpp in boosting the adaption of bacterial growth to nutrient downshift.

A From “feast” to “famine”, stringent response plays an important role in ensuring the timely adaption of bacterial growth to nutrient downshift. During amino acid downshift (rich medium to minimal medium), (p)ppGpp promotes the growth adaption of bacterial via activating amino acid biosynthesis. In the case of carbon downshift, the RelA-dependent (p)ppGpp stringent response maintains the transcription-translation coordination and further ensures the transcription processivity so that related catabolic proteins of specific carbons (e.g., lactose, glycerol and acetate) could be timely synthesized to allow bacteria to resume growth in the 2nd carbon source. B The physiological role of (p)ppGpp is a coin of two sides. On one hand, (p)ppGpp acts as a global suppressor of cell growth via shutting down various biochemical processes such as DNA replication, ribosome synthesis, translation (initiation and elongation) during stringent response. On the other hand, as shown in our studies, the (p)ppGpp’s role in activating amino acid biosynthesis and maintaining transcription processivity (via coordinating transcription-translation) is crucial for the timely adaption of bacterial growth to nutrient downshift.