Polyamines control inorganic polyphosphate levels during bacterial nitrogen starvation.

Inorganic polyphosphate (polyP) is a ubiquitous, multifunctional biomolecule that supports stress survival in bacteria. During nitrogen (N) starvation, Escherichia coli rapidly accumulates polyP, which drives the formation of RNA protein granules that sustain long term survival. What triggers this upregulation has remained unknown. Here we show that polyamines, a group of highly conserved, amino acid-derived polycations, regulate polyP accumulation during N starvation. We found that deleting all nine polyamine biosynthesis genes elevates polyP during exponential growth and by more than 5fold under N starvation, with shorter chains preferentially accumulating. To dissect which polyamine matters, we further deleted the three catabolic enzymes that consume polyamines as a nitrogen source, which enabled complementation assays. Supplying any one of the three physiological polyamines, putrescine, spermidine, or cadaverine, restored wild type polyP levels during N starvation. We found that the absence of polyamines did not affect the steady state levels of either the polyP synthesizing kinase PPK or the exopolyphosphatase PPX, pointing instead to posttranslational control of enzyme activity or to as yet unidentified polyamine dependent regulators. These findings establish a direct metabolic link between two universal, functionally intertwined biomolecules and suggest that the polyamine decline upon N starvation contributes to the observed polyP accumulation.