title: Zingerone silences quorum sensing and attenuates virulence of Pseudomonas aeruginosa.
abstract: Quorum sensing in Pseudomonas aeruginosa plays an imperative role in virulence factor, biofilm formation and antimicrobial resistance. Blocking quorum sensing pathways are viewed as viable anti-virulent therapy in association with traditional antimicrobial therapy. Anti-quorum sensing dietary phytochemicals with may prove to be a safe and viable choice as anti-virulent drug candidates. Previously, our lab proved zingerone as potent anti-biofilm agent hence; further its anti-virulent and anti-quorum activities were evaluated. Zingerone, besides decreasing swimming, swarming and twitching phenotypes of P. aeruginosa PAO1, reduced biofilm forming capacity and production of virulence factors including rhamnolipid, elastase, protease, pyocyanin, cell free and cell bound hemolysin (p<0.001) indicating anti-virulent property attributing towards attenuation of virulence of P. aeruginosa. Further zingerone not only had marked effect on the production of quorum sensing signal molecules by clinical isolates of P. aeruginosa but also showed significant interference with the activation of QS reporter strains. To study the mechanism of blocking quorum sensing cascade, in silico analysis was carried out. Anti-QS activity was attributed to interference with the ligand receptor interaction of zingerone with QS receptors (TraR, LasR, RhlR and PqsR). Zingerone showed a good comparative docking score to respective autoinducer molecules which was even higher than that of vanillin, a proven anti-quorum sensing phytochemical. The results of the present study revealed the anti-quorum sensing activity of zingerone targeting ligand-receptor interaction, hence proposing zingerone as a suitable anti-virulent drug candidate against P. aeruginosa infections.
authors.affiliation: Department of Microbiology, Panjab University, Chandigarh 160014, India.
authors.forename: Lokender
authors.initials: L
authors.lastname: Kumar
authors.affiliation: Department of Microbiology, Panjab University, Chandigarh 160014, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Chhibber
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Rajnish
authors.initials: R
authors.lastname: Kumar
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Microbiology, Panjab University, Chandigarh 160014, India. Electronic address: kusum_harjai@hotmail.com.
authors.forename: Kusum
authors.initials: K
authors.lastname: Harjai
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity; D053038:Quorum Sensing / Q000187:drug effects*; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; C013738:zingerone; D006139:Guaiacol
keywords: Antibiotic resistance; Biofilm formation; Phytochemical; Quorum sensing; Virulence; Zingerone