Metabolic control of the Escherichia coli universal stress protein response through fructose-6-phosphate.

The universal stress protein (Usp) superfamily encompasses a conserved group of proteins involved in stress resistance, adaptation to energy deficiency, cell motility and adhesion, and is found in all kingdoms of life. The paradigm usp gene, uspA, of Escherichia coli is transcriptionally activated by a large variety of stresses, and the alarmone ppGpp is required for this activation. Here, we show that the uspA gene is also regulated by an intermediate of the glycolytic/gluconeogenic pathways. Specifically, mutations and conditions resulting in fructose-6-phosphate (F-6-P) accumulation elicit superinduction of uspA upon carbon starvation, whereas genetic manipulations reducing the pool size of F-6-P have the opposite effect. This metabolic control of uspA does not act via ppGpp. Other, but not all, usp genes of the usp superfamily are similarly affected by alterations in F-6-P levels. We suggest that alterations in the pool size of phosphorylated sugars of the upper glycolytic pathway may ensure accumulation of required survival proteins preceding the complete depletion of the external carbon source. Indeed, we show that uspA is, in fact, induced before the carbon source is depleted from the medium.