期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 40, 页码 E9411-E9418出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1814023115
关键词
quorum sensing; biofilms; Pseudomonas aeruginosa; antimicrobial; virulence
资金
- Howard Hughes Medical Institute
- NIH Grant [5R37GM065859]
- National Science foundation [MCB-1713731]
- Life Science Research Foundation Postdoctoral Fellowship through the Gordon and Betty Moore Foundation [GBMF2550.06]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R37GM065859] Funding Source: NIH RePORTER
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 RhII/R, that produce and detect 3OC12-homoserine lactone and C4-homoserine lactone, respectively. Previously, we discovered that RhIR regulates both RhII-dependent and RhII-independent regulons, and we proposed that an alternative ligand functions together with RhIR to control the target genes in the absence of RhII. 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.
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