A tripartite RpoS-CRP-cAMP-Cra circuit orchestrates metabolic reprogramming during stress adaptation.

RpoS in Escherichia coli orchestrates a metabolic reprogramming by activating 667 genes, with metabolic genes surpassing stress-response targets in the regulon.

• Why it matters: Understanding how bacteria coordinate stress responses with metabolic demands is crucial for insights into bacterial survival and adaptation, yet this link remains poorly characterized.
• What they did: The study integrated RNA-seq, ChIP-seq, and molecular assays to redefine the RpoS regulon, revealing its role in activating glycolytic and sugar transport genes while repressing the TCA cycle and oxidative phosphorylation through a tripartite circuit.
• The result: This metabolic shift, regulated by the RpoS-CRP-cAMP-Cra circuit, enables energy-efficient survival during stationary phase and provides a mechanistic framework for transcriptional regulation based on promoter efficiency.