Polyamines control inorganic polyphosphate levels during bacterial nitrogen starvation

Abstract 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 5-fold 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 post-translational 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.