Targeting Polyphosphate Kinases in the Fight against Pseudomonas aeruginosa

Polyphosphate (polyP) is a universally conserved molecule that plays critical roles in managing bacterial stress responses, in addition to biofilm formation and virulence. The enzymes that make polyphosphate molecules are called polyphosphate kinases (PPKs). Since these enzymes are not conserved in higher eukaryotes, PPKs make excellent therapeutic targets. In a recent paper in mBio, Neville and colleagues described gallein, a commercially available G-protein antagonist, as a novel dual-specificity inhibitor against two families of PPK enzymes in Pseudomonas aeruginosa. In this commentary, we discuss the impact of this discovery, outline potential challenges of implementing gallein use in the clinic, and describe how gallein will serve as a fantastic new tool to further fundamental PPK and polyP research in bacteria.

Automated summary

Polyphosphate (polyP) is a conserved molecule that plays critical roles in bacterial stress responses, biofilm formation, and virulence. A recent study identified gallein as a dual-specificity inhibitor against two families of PPK enzymes in Pseudomonas aeruginosa. This discovery may provide a new tool for further research on fundamental PPK and polyP functions in bacteria.