PqsE adapts the activity of the quorum-sensing transcription factor RhlR to both autoinducer concentration and promoter sequence identity.

is an opportunistic human pathogen that poses a significant health threat. Many pathogenic behaviors of are under control of the bacterial cell-cell communication system known as quorum sensing (QS). One of the QS master regulators, RhlR, is a receptor/transcription factor that not only relies on binding of its canonical ligand, -butyrylhomoserine lactone (C4-HSL), but additionally requires a protein-protein interaction with the enzyme, PqsE. We constructed heterologous reporter strains in that allow measurements of the reliance of RhlR on C4-HSL and/or PqsE binding for the ability to activate transcription of three RhlR-regulated genes: (PqsE independent), (PqsE dependent), and (PqsE inhibited). Analogous assays measuring activation of the three genes in were performed, and the patterns observed correlated tightly with the heterologous reporter assays. These results confirm that the binding of PqsE to RhlR is able to fine-tune RhlR transcription factor activity in a promoter-specific manner and prove that this ability is independent of other factors present in .IMPORTANCE is an opportunistic human pathogen that can cause fatal infections. There exists an urgent need for new, effective antimicrobial agents to combat . The PqsE-RhlR protein-protein interaction is essential for to be able to make toxins, form biofilms, and infect host organisms. In this study, we use both non-native models in and measurements of gene expression/toxin production in to show that the PqsE-RhlR interaction enables fine-tuned gene expression and a heightened ability of to adapt to external conditions. These findings will be highly valuable as continued efforts are made to design inhibitors of the PqsE-RhlR interaction and test them as potential antimicrobial agents against infections.