Distal and proximal promoters co-regulatepqsRexpression inPseudomonas aeruginosa

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Abstract

Summary

The ubiquitous bacterium Pseudomonas aeruginosa is an opportunistic pathogen that can cause serious infections in immunocompromised individuals. P. aeruginosa virulence is controlled partly by intercellular communication, and the transcription factor PqsR is a necessary component in the P. aeruginosa cell-to-cell signaling network. PqsR acts as the receptor for the Pseudomonas quinolone signal, and it controls the production of 2-alkyl-4-quinolone molecules which are important for pathogenicity. Previous studies showed that the expression of pqsR is positively controlled by the quorum-sensing regulator LasR, but it was unclear how LasR is able to induce pqsR transcription. In this report, we further investigated the control of pqsR, and discovered two separate promoter sites that contribute to pqsR expression. LasR-mediated activation occurs at the distal promoter site, but this activation can be antagonized by the regulator CysB. The proximal promoter site also contributes to pqsR transcription, but initiation at this site is inhibited by a negative regulatory sequence element, and potentially by the H-NS family members MvaT and MvaU. We propose a model where positive and negative regulatory influences at each promoter site are integrated to modify pqsR expression. This arrangement could allow for information from both environmental signals and cell-to-cell communication to influence PqsR levels.

The opportunistic pathogen Pseudomonas aeruginosa coordinates the production of virulence factors by intercellular communication through several small molecules, including the Pseudomonas quinolone signal (PQS). We investigated pqsR regulation, and found that expression of the PQS receptor is controlled from two distinct promoter sites that can simultaneously contribute to pqsR transcription. Activation of the distal promoter has the most significant effects on pqsR expression, but more proximal regulatory elements allow multiple factors to modulate PqsR levels.

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