Clove bud oil reduces kynurenine and inhibits pqs A gene expression in P. aeruginosa

• Published in: Applied microbiology and biotechnology 2016-04, Vol.100 (8), p.3681-3692
• Main Authors: H., Jayalekshmi, Omanakuttan, Athira, Pandurangan, N, S. Vargis, Vidhu, Maneesh, M, G. Nair, Bipin, B. Kumar, Geetha
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; Applied Microbial and Cell Physiology; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; biofilm; Biofilms; Biofilms - drug effects; Biomedical and Life Sciences; Biotechnology; Clove Oil - pharmacology; Cloves; communications technology; DNA; dose response; Down-Regulation - drug effects; Drug resistance; Essences and essential oils; Essential oils; Eugenia; eugenol; exopolysaccharides; Gene expression; Gene Expression Regulation, Bacterial - drug effects; genes; Genetic aspects; Health aspects; Host-bacteria relationships; hydrogen bonding; hydrophobic bonding; in vitro studies; kynurenine; Kynurenine - metabolism; Life Sciences; Microbial Genetics and Genomics; Microbiology; Motility; multiple drug resistance; Nosocomial infections; Observations; oils; Pathogens; Prevention; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - physiology; quorum sensing; Quorum Sensing - drug effects; signal transduction; Studies; swine; Virulence
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-016-7313-2

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.