Schematic representation of the pqs QS system in P. aeruginosa.

The core of the pqs QS system is composed of the pqsABCDE-phnAB operon and the pqsR gene. Proteins coded by the pqsABCDE-phnAB operon synthesize HHQ that binds to and activates PqsR. The PqsR-HHQ complex promotes PpqsA activity, thus increasing HHQ and PqsE levels. Notably, the PpqsA promoter is the only target of the PqsR-HHQ complex. Apart from its contribution to HHQ biosynthesis, PqsE influences the P. aeruginosa transcriptome via a still uncharacterized AQ-independent pathway(s). In this way, PqsE up-regulates the expression of genes involved in virulence factor production, biofilm development, and antibiotic resistance. Conversely, PqsE down-regulates PpqsA activity, AQ production and the expression of genes involved in denitrification and T6SS. The pqsH and pqsL genes are required for PQS and HQNO biosynthesis, respectively. HQNO did not affect the P. aeruginosa transcriptome, and probably contributes to environmental competition due to its cytochrome inhibitory activity. PQS chelates iron triggering the iron-starvation response and increasing the transcription of virulence factor genes coding for virulence factors such as pyoverdine, ExoS toxin and AprX protease. Moreover, PQS down-regulates genes involved in denitrification. Most of the regulatory effects exerted by PQS are PqsR-independent, since the PqsR-PQS (or PqsR-HHQ) complex only promotes PpqsA activity. However, PQS also increases PpqsA and PpqsR expression via a PqsR-independent pathway(s) that is unrelated to the iron-starvation response, but is inhibited in the presence of high-iron concentrations. Dotted grey arrows indicate gene expression; solid grey arrows represent biosynthesis; solid black arrow indicates PqsR-dependent activation (+); dashed black arrows indicate PqsR-independent activation (+); black T-line indicates negative regulation (-); dashed grey arrows represent information flow.