Naturally Occurring Quorum Sensing Inhibitors for Pseudomonas aeruginosa by Molecular Modeling

Abstract

The quorum-sensing (QS) system allows organisms to communicate and form virulence factors such as biofilm. Pseudomonas aeruginosa is one of the Gram-negative bacteria leaving many casualties every year. In the past years, the bacteria's QS system has gained attention as a valuable target to design and develop new efficient antibiotics. Nature has always been an inspiration source for designing many new medicines, and using natural compounds is always the first approach to discover and design new drugs. Here, we in-silico studied 24,000 natural compounds, including first and secondary metabolites, on five known QS-related receptors of Pseudomonas aeruginosa. After several levels of screening, compounds NP-1 (3,6′-di-O-sinapoylsucrose), NP-2 (ZINC000257412737), NP-3 (3-O-β-D-rutinosin) showed the best inhibition activity on AHL synthase LasI with the docking scores of-8.988,-8.690, and-8.925 kcal/mol, respectively. Also, NP-101 (ZINC000077264779), NP-102 (ZINC000225518732), and NP-103 (ZINC000096269362) were selected for LasR-LBD with the scores of-13.355,-13.038, and-12.917 kcal/mol, respectively. In the case of LasA, docking scores of-13.357,-10.796, and-10.564 kcal/mol were obtained for NP-201 (Parishin), NP-202 (7-O-galloyl-D-sedoheptulose), and NP-203 (1,2-di-O-galloyl-6-O-p-coumaroyl-β-D-glucose), respectively. Furthermore, when the LasR-TP4 was the target, the best results were observed from NP-301 (ZINC000514288841), NP-302 (ZINC000077264754), and again NP-103 (ZINC000096269362), in which they showed docking scores of-13.175,-13.020, and-12.998 kcal/mol, respectively. Finally, the highest docking scores belonged to NP-401 (ZINC000150351649), NP-402 (ZINC000150351636), NP-403 (ZINC000150349056), which interacted with the ATPase Type IV pilus with the docking scores of-16.274,-15.773, and-15.405 kcal/mol, respectively.