A New Transcriptional Repressor of the Pseudomonas aeruginosa Quorum Sensing Receptor Gene lasR

Pseudomonas aeruginosa pathogenic potential is controlled via multiple regulatory pathways, including three quorum sensing (QS) systems. LasR is a key QS signal receptor since it acts as a global transcriptional regulator required for optimal expression of main virulence factors. P. aeruginosa modulates the QS response by integrating this cell density-dependent circuit to environmental and metabolic cues. Hence, QS also controls the adaptation to challenging environmental niches, such as infection sites. However, little is known about the molecular mechanisms connecting QS and other signalling pathways. In this work, DNA-affinity chromatography was used to identify new lasR transcriptional regulators. This approach led to the identification and functional characterization of the TetR-like transcriptional repressor PA3699. This protein was purified and shown to directly bind to the lasR promoter region in vitro. The induction of PA3699 expression in P. aeruginosa PAO1 cultures repressed lasR promoter activity and the production of LasR-dependent virulence factors, such as elastase, pyocyanin, and proteases. These findings suggest a role for PA3699 in P. aeruginosa pathogenicity. P. aeruginosa genome encodes at least 38 TetR-family proteins, and PA3699 is the eighth member of this group functionally characterized so far and the first one shown to bind the lasR promoter in vitro.