Isonitrile-functionalized tyrosine modulates swarming motility and quorum sensing in Pseudomonas aeruginosa

Paerucumarin synthesized by pvc operon pvcABCD is an iron binding molecule which modulates biofilm formation in Pseudomonas aeruginosa but its direct function in bacterial pathogenesis needs further investigation. pvcA synthesizes isonitrile functionalized tyrosine (IFT) which is converted to mature paerucumarin by the proteins encoded by pvcB, pvcC and pvcD genes. Interruption of pvcB in MPAO1 resulted in accumulation of IFT as it cannot be converted to mature molecule. The MPAO1 pvcB mutant (PW4832) showed enhanced swarming motility, while complementation with plasmid pLL2 carrying pvcB reduced swarming motility. Enhanced levels of rhlA expression and rhamnolipid production were observed in PW4832 compared to the parent strain. Overexpression of ptxR, the positive regulator of pvcABCD, in PW4832 caused accumulation of more IFT and further elevated the level of rhlA expression. Expression of the quorum sensing system transcriptional activators lasR and rhlR, as well as the synthase genes lasI and rhlI, was enhanced in PW4832 compared to MPAO1, as was PQS accumulation. Exogenously added IFT, but not paerucumarin, enhanced the production of rhamnolipids in P. aeruginosa. These results suggest that IFT enhances swarming motility in P. aeruginosa either directly by enhancing rhamnolipid production or indirectly through modulation of the quorum sensing systems. This is the first report assigning an independent function to IFT in P. aeruginosa.