title: Clove bud oil reduces kynurenine and inhibits pqs A gene expression in P. aeruginosa.
abstract: Quorum sensing (QS), a communication system involved in virulence of pathogenic bacteria like Pseudomonas aeruginosa is a promising target to combat multiple drug resistance. In vitro studies using clove bud oil (CBO) in P. aeruginosa revealed a concentration dependent attenuation of a variety of virulence factors including motility, extracellular DNA, exopolysaccharides and pigment production. Furthermore, treatment with CBO demonstrated a distinct dose-dependent reduction in biofilm formation as well as promoting dispersion of already formed biofilm, observations that were also supported by porcine skin ex vivo studies. Expression studies of genes involved in signalling systems of P. aeruginosa indicated a specific decrease in transcription of pqsA, but not in the lasI or rhlI levels. Additionally, the expression of vfr and gacA genes, involved in regulation, was also not affected by CBO treatment. CBO also influenced the PQS signalling pathway by decreasing the levels of kynurenine, an effect which was reversed by the addition of exogenous kynurenine. Though the synthesis of the signalling molecules of the Las and Rhl pathways was not affected by CBO, their activity was significantly affected, as observed by decrease in levels of their various effectors. Molecular modelling studies demonstrated that eugenol, the major component of CBO, favourably binds to the QS receptor by hydrophobic interactions as well as by hydrogen bonding with Arg61 and Tyr41 which are key amino acid residues of the LasR receptor. These results thus elucidate the molecular mechanism underlying the action of CBO and provide the basis for the identification of an attractive QS inhibitor.
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Clappana P. O, Kollam, Kerala, 690525, India.
authors.forename: Jayalekshmi
authors.initials: J
authors.lastname: H
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Clappana P. O, Kollam, Kerala, 690525, India.
authors.forename: Athira
authors.initials: A
authors.lastname: Omanakuttan
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Clappana P. O, Kollam, Kerala, 690525, India.
authors.forename: N
authors.initials: N
authors.lastname: Pandurangan
authors.affiliation: Department of Sciences, Amrita Vishwa Vidyapeetham, Amritanagar P. O, Coimbatore, 641112, India.
authors.forename: Vidhu
authors.initials: V
authors.lastname: S Vargis
authors.affiliation: Pushpagiri Institute of Medical Sciences and Research Centre, Tiruvalla, Kerala, 689101, India.
authors.forename: M
authors.initials: M
authors.lastname: Maneesh
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Clappana P. O, Kollam, Kerala, 690525, India.
authors.forename: Bipin
authors.initials: B
authors.lastname: G Nair
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Clappana P. O, Kollam, Kerala, 690525, India. ammasgeeta@gmail.com.
authors.forename: Geetha
authors.initials: G
authors.lastname: B Kumar
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects; D045783:Clove Oil / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D007737:Kynurenine / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D053038:Quorum Sensing / Q000187:drug effects
chemical_list: D001426:Bacterial Proteins; D045783:Clove Oil; D007737:Kynurenine
keywords: Biofilm; Clove bud oil; P. aeruginosa; Quorum sensing