SUMMARYBacteria are constantly exposed to changing environmental conditions, and to survive they need to adapt quickly, adjusting their gene expression and metabolism to make the most of the resources available. One of the mechanisms involved is the stringent response, characterized by production of specific guanosine derivatives-ppGpp and pppGpp (collectively called (p)ppGpp). These regulators exert their action and coordinate a global response at many different levels, for example, transcription, translation, nucleotide metabolism, DNA replication, and carbon and lipid metabolism. In this review, we discuss how (p)ppGpp is synthesized and degraded, how it controls different cellular processes and their interplay with other second messengers. A description of differences in (p)ppGpp regulation in Gram-negative and Gram-positive bacteria, along with recent findings and some historical perspectives, is provided. We argue that although much is known about the stringent response and the novel discoveries are definitely advancing the (p)ppGpp field, they are not exhaustive. Instead, they seem to constantly point to aspects that are still waiting to be uncovered-thus, the (p)ppGpp magic goes on.
Potrykus et al. (2026) studied this question.