The Gac/Rsm and cyclic‐di‐GMP signalling networks coordinately regulate iron uptake in Pseudomonas aeruginosa

Summary P seudomonas aeruginosa is a versatile bacterial pathogen capable of occupying diverse ecological niches. To cope with iron limitation, P . aeruginosa secretes two siderophores, pyoverdine and pyochelin, whose ability to deliver iron to the cell is crucial for biofilm formation and pathogenicity. In this study, we describe a link between iron uptake and the G ac/ R sm system, a conserved signal transducing pathway of P . aeruginosa that controls the production of extracellular products and virulence factors, as well as the switch from planktonic to biofilm lifestyle. We have observed that pyoverdine and pyochelin production in P . aeruginosa is strongly dependent on the activation state of the G ac/ R sm pathway, which controls siderophore regulatory and biosynthetic genes at the transcriptional level, in a manner that does not involve regulation of ferric uptake regulator ( F ur) expression. G ac/ R sm‐mediated regulation of iron uptake genes appears to be conserved in different P . aeruginosa strains. Further experiments led to propose that the G ac/ R sm system regulates siderophore production through modulation of the intracellular levels of the second messenger c‐di‐ GMP , indicating that the c‐di‐ GMP and the G ac/ R sm regulatory networks essential for biofilm formation can also coordinately control iron uptake in P . aeruginosa .