The PqsE and RhlR proteins are an autoinducer synthase–receptor pair that control virulence and biofilm development inPseudomonas aeruginosa

Significance The human pathogen Pseudomonas aeruginosa is the leading cause of hospital-acquired infections and, moreover, is resistant to commonly used antibiotics. P. aeruginosa uses the cell-to-cell communication process called quorum sensing (QS) to control virulence. QS relies on production and response to extracellular signaling molecules called autoinducers. Here, we identify the PqsE enzyme as the synthase of an autoinducer that activates the QS receptor RhlR. We show that the PqsE-derived autoinducer is the key molecule driving P. aeruginosa biofilm formation and virulence in animal models of infection. We propose that PqsE and RhlR constitute a QS synthase–receptor pair, and that this system can be targeted for antimicrobial development.