, 2003; Glansdorp et al , 2004; Rasmussen et al , 2005) Recently

, 2003; Glansdorp et al., 2004; Rasmussen et al., 2005). Recently, several crystal structures of the quorum-sensing regulatory proteins with their cognate AIs have been reported

(Vannini et al., 2002; Bottomley et al., 2007; De Silva et al., 2007; Kim et al., 2010), and in line C59 wnt with that computational modelling approaches have been employed to design potential QSIs. Yang et al. (2009a b) applied molecular docking and virtual screening and identified three recognized drugs, salicylic acid, nifuroxazide, and chlorzoxazone, as QSIs of P. aeruginosa (Yang et al., 2009a b). AI structurally unrelated QSIs were discovered by Soulere et al. (2010) through docking-based screening on a 2344 chemical compounds library (Soulere et al., 2010). Besides docking, structure-activity relationship methods

are also applied to design and identify novel QSIs (Steenackers et al., 2010; Brackman et al., 2011). Over the past few years, researchers have identified quorum-quenching enzymes from many prokaryotic and eukaryotic organisms, which degrade quorum-sensing signal molecules (Dong et al., 2007). Bacillus spp. produces a N-acyl-homoserine lactone lactonase that hydrolyses this major group quorum sensing AI in Gram-negative Carfilzomib mouse bacteria (Augustine et al., 2010). Mammalian cells was shown to produce paraoxonases (PON1, PON2, and PON3) that hydrolytically inactivate quorum sensing signal N-(3-oxododecanoyl)-l-homoserine lactone from P. aeruginosa (Teiber et al., 2008). Recently, metagenomic approaches are widely applied to identify novel enzymes from nature. Bijtenhoorn et al. (2011) isolated and biochemically characterized SPTLC1 a novel N-acyl-homoserine lactone hydrolase, BpiB05, from the soil metagenome (Bijtenhoorn et al., 2011). BpiB05 is not distantly related to any of the currently

known N-acyl-homoserine lactone hydrolases and strongly reduces motility, pyocyanin synthesis and biofilm formation by P. aeruginosa (Bijtenhoorn et al., 2011). Quorum-quenching enzymes have been immobilized on surfaces and applied as anti-biofilm agents (Kim et al., 2011; Ng et al., 2011). Secondary metabolites may serve as intercellular pathogenic signals, which regulate numerous phenomena including biofilm formation (Dufour & Rao, 2011). Thus, metabolic intervention can be used to affect development and differentiation of biofilms. The green tea epigallocatechin gallate was shown to reduce both quorum sensing and biofilm development of P. aeruginosa through inhibiting the enoyl-acyl carrier protein reductase from the type II fatty acid synthesis pathway (Yang et al., 2010). A cyclopropane-containing fatty acid, lyngbyoic acid, from the marine cyanobacterium was shown to directly inhibit LasB enzymatic activity and reduce the production of pyocyanin and elastase in P. aeruginosa (Kwan et al., 2011).

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