Polyphosphate kinase is essential for biofilm development, quorum sensing,and virulence of Pseudomonas aeruginosa

The human opportunistic pathogen Pseudomonas aeruginosa causes a variety of infections in immunocompromised hosts and in individuals with cystic: fibr osis. A knockout mutation in the polyphosphate kinase (ppk) gene, encoding PPK responsible for the synthesis of inorganic polyphosphate from ATP, rend ers P. aeroginosa cells unable to form a thick and differentiated biofilm. The mutant is aberrant in quorum sensing and responses in that production o f the quorum-sensing controlled virulence factors elastase and rhamnolipid are severely reduced. In a burned-mouse pathogenesis model, the virulence o f the mutant is greatly reduced with severe defects in the colonization of mouse tissues. The conservation of PPK among many bacterial pathogens and i ts absence in eukaryotes suggest that PPK might be an attractive target for antimicrobial drugs.