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

• Type of Material: Article
• Authors: Sampriti Mukherjee, Princeton University; Dina A. Moustafa, Emory University; Vasiliki Stergioula, Princeton University; Chari D. Smith, Princeton University; Joanna B. Goldberg, Emory University; Bonnie L. Bassler, Princeton University
• Language: English
• Date: 2018-10-02
• Publisher: National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: © 2018 the Author(s). Published by PNAS.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1814023115
• Title of Journal or Parent Work: Proceedings of the National Academy of Sciences
• ISSN: 0027-8424
• Volume: 115
• Issue: 40
• Start Page: E9411
• End Page: E9418
• Grant/Funding Information: This work was supported by the Howard Hughes Medical Institute, NIH Grant 5R37GM065859, and National Science foundation Grant MCB-1713731 (to B.L.B.), and a Life Science Research Foundation Postdoctoral Fellowship through the Gordon and Betty Moore Foundation through Grant GBMF2550.06 (to S.M.).
• Keywords: Pseudomonas aeruginosa; quorum sensing; biofilms; virulence; antimicrobial
• Research Categories: Biology, Molecular

Abstract

Pseudomonas aeruginosa is a leading cause of life-threatening nosocomial infections. Many virulence factors produced by P. aeruginosa are controlled by the cell-to-cell communication process called quorum sensing (QS). QS depends on the synthesis, release, and groupwide response to extracellular signaling molecules called autoinducers. P. aeruginosa possesses two canonical LuxI/R-type QS systems, LasI/R and RhlI/R, that produce and detect 3OC12-homoserine lactone and C4-homoserine lactone, respectively. Previously, we discovered that RhlR regulates both RhlI-dependent and RhlI-independent regulons, and we proposed that an alternative ligand functions together with RhlR to control the target genes in the absence of RhlI. Here, we report the identification of an enzyme, PqsE, which is the alternative-ligand synthase. Using biofilm analyses, reporter assays, site-directed mutagenesis, protein biochemistry, and animal infection studies, we show that the PqsE-produced alternative ligand is the key autoinducer that promotes virulence gene expression. Thus, PqsE can be targeted for therapeutic intervention. Furthermore, this work shows that PqsE and RhlR function as a QS-autoinducer synthase–receptor pair that drives group behaviors in P. aeruginosa.