title: Computational discovery of putative quorum sensing inhibitors against LasR and RhlR receptor proteins of Pseudomonas aeruginosa.
abstract: Drugs have been discovered in the past mainly either by identification of active components from traditional remedies or by unpredicted discovery. A key motivation for the study of structure based virtual screening is the exploitation of such information to design targeted drugs. In this study, structure based virtual screening was used in search for putative quorum sensing inhibitors (QSI) of Pseudomonas aeruginosa. The virtual screening programme Glide version 5.5 was applied to screen 1,920 natural compounds/drugs against LasR and RhlR receptor proteins of P. aeruginosa. Based on the results of in silico docking analysis, five top ranking compounds namely rosmarinic acid, naringin, chlorogenic acid, morin and mangiferin were subjected to in vitro bioassays against laboratory strain PAO1 and two more antibiotic resistant clinical isolates, P. aeruginosa AS1 (GU447237) and P. aeruginosa AS2 (GU447238). Among the five compounds studied, except mangiferin other four compounds showed significant inhibition in the production of protease, elastase and hemolysin. Further, all the five compounds potentially inhibited the biofilm related behaviours. This interaction study provided promising ligands to inhibit the quorum sensing (QS) mediated virulence factors production in P. aeruginosa.
authors.affiliation: Department of Biotechnology, Alagappa University, Karaikudi, 630 003, Tamil Nadu, India.
authors.forename: Angusamy
authors.initials: A
authors.lastname: Annapoorani
authors.forename: Venugopal
authors.initials: V
authors.lastname: Umamageswaran
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Parameswari
authors.forename: Shunmugiah Karutha
authors.initials: SK
authors.lastname: Pandian
authors.forename: Arumugam Veera
authors.initials: AV
authors.lastname: Ravi
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000254:growth & development / Q000378:metabolism*; D053038:Quorum Sensing; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; C080365:LasR protein, Pseudomonas aeruginosa; D015534:Trans-Activators