Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target

YesN-acylhomoserine lactone (AHL)-based quorum sensing (QS) is important for the regulation of proteobacterial virulence determinants. Thus, the inhibition of AHL synthases offers non-antibiotics-based therapeutic potentials against QS-mediated bacterial infections. In this work, functional AHL synthases of Pseudomonas aeruginosa LasI and RhlI were heterologously expressed in an AHL-negative Escherichia coli followed by assessments on their AHLs production using AHL biosensors and high resolution liquid chromatography–mass spectrometry (LCMS). These AHL-producing E. coli served as tools for screening AHL synthase inhibitors. Based on a campaign of screening synthetic molecules and natural products using our approach, three strongest inhibitors namely are salicylic acid, tannic acid and trans-cinnamaldehyde have been identified. LCMS analysis further confirmed tannic acid and trans-cinnemaldehyde efficiently inhibited AHL production by RhlI. We further demonstrated the application of trans-cinnemaldehyde inhibiting Rhl QS system regulated pyocyanin production in P. aeruginosa up to 42.06%. Molecular docking analysis suggested that trans-cinnemaldehyde binds to the LasI and EsaI with known structures mainly interacting with their substrate binding sites. Our data suggested a new class of QS-inhibiting agents from natural products targeting AHL synthase and provided a potential approach for facilitating the discovery of anti-QS signal synthesis as basis of novel anti-infective approach.University of Malaya High Impact Research (HIR) Grant (UM-MOHE HIR Grant UM.C/625/1/HIR/MOHE/CHAN/14/1, no. H-50001-A000027) given to K.G.C. and National Natural Science Foundation of China (no. 81260481) given to H.W

SODIUM DODECYL-SULFATE INDUCED ENHANCEMENT OF THE VISCOSITY AND VISCOELASTICITY OF AQUEOUS-SOLUTIONS OF POLY(ETHYLENE OXIDE) - A RHEOLOGICAL STUDY ON POLYMER MICELLE INTERACTION

A large enhancement of the viscosity and the viscoelasticity of aqueous solutions of high molecular weight poly(ethylene oxide) (PEO) has been observed upon addition of sodium dodecyl sulfate (SDS). The changes in apparent viscosity, in the parameters for the power law model of non-Newtonian behavior, and in the viscoelasticity start at the critical concentration for formation of polymer-bound micelles and level off above the saturation concentration. These phenomena are attributed to coil expansion of PEO induced by binding of SDS micelles onto the polymer. At high SDS concentration and high shear rate, the normal stress difference, which is a measure of the viscoelasticity, becomes almost independent of shear rate. This peculiar behavior is proposed to arise from partial shear-induced breakdown of the polymer-micelle complexes

INFLUENCE OF POLYMERS ON THE MICELLIZATION OF CETYLTRIMETHYLAMMONIUM SALTS

The critical micelle concentration values and aggregation numbers of cetyltrimethylammonium bromide (CTAB) micelles have been measured in the presence and absence of the polymers poly(vinyl methyl ether) (PVME), poly(propylene oxide) (PPO), poly(ethylene oxide) (PEO), and poly(vinylpyrrolidone) (PVP). Association of the micelles with the polymers PVME and PPO is apparent from a reduction in both the cmc and the aggregation number. PEO and PVP do not influence these properties. The influence of PVME on the transition from spherical to rodlike micelles of cetyltrimethylammonium tosylate (CTATs) has been studied by measuring viscosities. The shift to higher concentrations of the sudden viscosity increase in the presence of PVME is interpreted as resulting from the formation of spherical, polymer-bound micelles in preference to rodlike micelles. A similar interpretation applies to the transformation of a viscous and non-Newtonian solution of CTAB/sodium salicylate (NaSal) into a waterlike, Newtonian fluid upon addition of PPO or PVME. PVP, ethanol, and 2-methyl-2-propanol do not influence the rheology of a CTAB/NaSal solution, but PEO exerts a modest effect

EFFECT OF SURFACTANT CHARGE ON POLYMER MICELLE INTERACTION - N-DODECYLDIMETHYLAMINE OXIDE

The influence of the nonionic water-soluble polymers poly(vinyl methyl ether) (PVME), poly(propylene oxide) (PPO), and poly(ethylene oxide) (PEO) on the aggregation behavior of n-dodecyldimethylamine oxide (DDAO), at various stages of protonation, has been studied. Critical micelle concentration (cmc) values were determined by the pH method and revealed an increase in stabilization of the micelles by association with PVME and PPO, upon increasing the average charge of the surfactant. The micelles formed from nonionic DDAO are not stabilized by association with PVME or PPO, but association was apparent from the reduction in aggregation number. This reduction in aggregation number is even more pronounced at higher surfactant charge. The results are interpreted in terms of a reduction in electrostatic inter-head-group interaction upon formation of the smaller polymer-bound micelles in the case of the charged surfactant molecules. PEO does not exert any influence on either the cmc or the aggregation number of DDAO micelles at any degree of protonation indicating the absence of polymer-micelle interaction. The effect of neutral and protonated DDAO on the clouding behavior of PVME and PPO has also been studied.</p