PqsE acts as an adaptor protein for the quorum-sensing transcription factor RhlR in Pseudomonas aeruginosa
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Pseudomonas aeruginosa is a human pathogen that poses a significant health threat. Pathogenic behaviors of P. aeruginosa 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, C4-homoserine lactone (HSL), but additionally requires a protein-protein interaction with the enzyme, PqsE. We constructed heterologous reporter strains in Escherichia coli 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: rhlA (PqsE-independent), phzM (PqsE-dependent), and azeB (PqsE-suppressed). Analogous assays measuring activation of the three genes in P. aeruginosa were performed and the patterns observed correlated tightly with the heterologous reporter assays. These results indicate that binding of PqsE to RhlR is able to fine-tune RhlR transcription factor activity in a promoter-specific manner.
Importance
Pseudomonas aeruginosa is an opportunistic human pathogen that can cause fatal infections. There exists an urgent need for new, effective antimicrobial agents to combat P. aeruginosa . The PqsE-RhlR protein-protein interaction is essential for P. aeruginosa to be able to make toxins, form biofilms, and infect host organisms. In this study, we use both non-native models in E. coli and measurements of gene expression/toxin production in P. aeruginosa to show that the PqsE-RhlR interaction enables fine-tuned gene expression and a heightened ability of P. aeruginosa 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 P. aeruginosa infections.
