title: Investigation of Pseudomonas aeruginosa quorum-sensing signaling system for identifying multiple inhibitors using molecular docking and structural analysis methodology.
abstract: Pseudomonas aeruginosa is an opportunistic human pathogen and a common Gram-negative bacterium in hospital-acquired infections. It causes death in many burn victims, cystic-fibrosis and neutropenic-cancer patients. It is known that P. aeruginosa biofilm maturation and production of cell-associated and extracellular virulence factors such as pyocyanin, elastase and rhamnolipids are under the control of a quorum-sensing (QS) system. Among several proteins involved in the Pseudomonas QS mechanism, LasR and PqsE play an important role in its cascade signaling system. They can cause increases in QS factors, biofilm maturation, and the production of virulence factors. Therefore, inhibition of these proteins can reduce the pathogenicity of P. aeruginosa. According to the structure of corresponding auto-inducers bound to these proteins, in silico calculations were performed with some non-steroidal anti-inflammatory drugs (NSAIDs) to estimate possible interactions and find the co-inhibitors of LasR and PqsE. The results showed that oxicams (Piroxicam and Meloxicam) can interact well with active sites of both proteins with the Ki of 119.43 nM and 4.0 μM for Meloxicam and 201.39 nM and 4.88 μM against LasR and PqsE, respectively. These findings suggested that Piroxicam and Meloxicam can be used as potential inhibitors for control of the P. aeruginosa QS signaling system and biofilm formation, and may be used in the design of multiple inhibitors.
authors.affiliation: Department of Drug and Food Control, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Soheili
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Bibi Sedigheh Fazly
authors.initials: BS
authors.lastname: Bazzaz
authors.affiliation: Department of Biology, Faculty of Sciences, Young Researchers and Elite Club, Islamic Azad University-Mashhad Branch, Mashhad, Iran.
authors.forename: Nooshin
authors.initials: N
authors.lastname: Abdollahpour
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Hadizadehf@mums.ac.ir.
authors.forename: Farzin
authors.initials: F
authors.lastname: Hadizadeh
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D062105:Molecular Docking Simulation; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D053038:Quorum Sensing
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins
keywords: Biofilm; Docking; NSAID; Pseudomonas aeruginosa; Quorum sensing