QapR (PA5506) Represses an Operon That Negatively Affects the Pseudomonas Quinolone Signal in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that can cause disease in varied sites within the human body and is a significant source of morbidity and mortality in those afflicted with cystic fibrosis.P. aeruginosa is able to coordinate group behaviors, such as virulence factor production, through the process of cell-to-cell signaling. There are three intercellular signaling systems employed byP. aeruginosa , and one of these systems utilizes the small molecule 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas quinolone signal [PQS]). PQS is required for virulence in multiple infection models and has been found in the lungs of cystic fibrosis patients colonized byP. aeruginosa . In this study, we have identified an RpiR family transcriptional regulator, QapR, which is an autoregulatory repressor. We found that mutation ofqapR caused overexpression of theqapR operon. We characterized theqapR operon to show that it contains genesqapR , PA5507, PA5508, and PA5509 and that QapR directly controls the transcription of these genes in a negative manner. We also show that derepression of this operon greatly reduces PQS concentration inP. aeruginosa . Our results suggest thatqapR affects PQS concentration by repressing an enzymatic pathway that acts on PQS or a PQS precursor to lower the PQS concentration. We believe that this operon comprises a novel mechanism to regulate PQS concentration inP. aeruginosa .