Dynorphin Activates Quorum Sensing Quinolone Signaling in Pseudomonas Aeruginosa

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2007 Mar 21

PMID 17367209

Citations 94

Authors

Olga Zaborina

Francois Lepine

Gaoping Xiao

Vesta Valuckaite

Yimei Chen

Terry Li

Mae Ciancio

Alex Zaborin

Elaine O Petrof

Elaine Petroff

Jerrold R Turner

Laurence G Rahme

Eugene Chang

John C Alverdy

Affiliations

Soon will be listed here.

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.

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