title: The role of 2,4-dihydroxyquinoline (DHQ) in Pseudomonas aeruginosa pathogenicity.
abstract: Bacteria synchronize group behaviors using quorum sensing, which is advantageous during an infection to thwart immune cell attack and resist deleterious changes in the environment. In Pseudomonas aeruginosa, the Pseudomonas quinolone signal (Pqs) quorum-sensing system is an important component of an interconnected intercellular communication network. Two alkylquinolones, 2-heptyl-4-quinolone (HHQ) and 2-heptyl-3-hydroxy-4-quinolone (PQS), activate transcriptional regulator PqsR to promote the production of quinolone signals and virulence factors. Our work focused on the most abundant quinolone produced from the Pqs system, 2,4-dihydroxyquinoline (DHQ), which was shown previously to sustain pyocyanin production and antifungal activity of P. aeruginosa. However, little is known about how DHQ affects P. aeruginosa pathogenicity. Using C. elegans as a model for P. aeruginosa infection, we found pqs mutants only able to produce DHQ maintained virulence towards the nematodes similar to wild-type. In addition, DHQ-only producing mutants displayed increased colonization of C. elegans and virulence factor production compared to a quinolone-null strain. DHQ also bound to PqsR and activated the transcription of pqs operon. More importantly, high extracellular concentration of DHQ was maintained in both aerobic and anaerobic growth. High levels of DHQ were also detected in the sputum samples of cystic fibrosis patients. Taken together, our findings suggest DHQ may play an important role in sustaining P. aeruginosa pathogenicity under oxygen-limiting conditions.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina , Charleston, SC , United States.
authors.forename: Jordon D
authors.initials: JD
authors.lastname: Gruber
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina , Charleston, SC , United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina , Charleston, SC , United States.
authors.forename: Stuart
authors.initials: S
authors.lastname: Parnham
authors.affiliation: Natural Products Chemistry, National Ocean Service , Charleston, SC , United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Beauchesne
authors.affiliation: Natural Products Chemistry, National Ocean Service , Charleston, SC , United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Moeller
authors.affiliation: Department of Medicine, Medical University of South Carolina , Charleston, SC , United States.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Flume
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina , Charleston, SC , United States.
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Zhang
keywords: Cystic fibrosis; Pathogenicity; Pseudomonas aeruginosa; Pseudomonas quinolone signal; Quorum sensing; Transcriptional regulation