title: Dynorphin activates quorum sensing quinolone signaling in Pseudomonas aeruginosa.
abstract: There is now substantial evidence that compounds released during host stress directly activate the virulence of certain opportunistic pathogens. Here, we considered that endogenous opioids might function as such compounds, given that they are among the first signals to be released at multiple tissue sites during host stress. We tested the ability of various opioid compounds to enhance the virulence of Pseudomonas aeruginosa using pyocyanin production as a biological readout, and demonstrated enhanced virulence when P. aeruginosa was exposed to synthetic (U-50,488) and endogenous (dynorphin) kappa-agonists. Using various mutants and reporter strains of P. aeruginosa, we identified involvement of key elements of the quorum sensing circuitry such as the global transcriptional regulator MvfR and the quorum sensing-related quinolone signaling molecules PQS, HHQ, and HQNO that respond to kappa-opioids. The in vivo significance of kappa-opioid signaling of P. aeruginosa was demonstrated in mice by showing that dynorphin is released from the intestinal mucosa following ischemia/reperfusion injury, activates quinolone signaling in P. aeruginosa, and enhances the virulence of P. aeruginosa against Lactobacillus spp. and Caenorhabditis elegans. Taken together, these data demonstrate that P. aeruginosa can intercept opioid compounds released during host stress and integrate them into core elements of quorum sensing circuitry leading to enhanced virulence.
authors: Department of Surgery, Pritzker School of Medicine, University of Chicago, Chicago, Illinois, United States of America.
authors: Olga
authors: O
authors: Zaborina
authors: Francois
authors: F
authors: Lepine
authors: Gaoping
authors: G
authors: Xiao
authors: Vesta
authors: V
authors: Valuckaite
authors: Yimei
authors: Y
authors: Chen
authors: Terry
authors: T
authors: Li
authors: Mae
authors: M
authors: Ciancio
authors: Alex
authors: A
authors: Zaborin
authors: Elaine O
authors: EO
authors: Petrof
authors: Elaine
authors: E
authors: Petroff
authors: Jerrold R
authors: JR
authors: Turner
authors: Laurence G
authors: LG
authors: Rahme
authors: Eugene
authors: E
authors: Chang
authors: John C
authors: JC
authors: Alverdy
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D011710:Pyocyanine / Q000096:biosynthesis; D015363:Quinolones / Q000378:metabolism*; D053038:Quorum Sensing / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D014774:Virulence
chemical_list: C407944:2-heptyl-3-hydroxy-4-quinolone; D015363:Quinolones; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; D011710:Pyocyanine