Screening of SdiA Inhibitors from Melia dubia Seeds Extracts Towards the Hold Back of Uropathogenic E.coli Quorum Sensing-Regulated Factors

Abstract

Plants have always been a supreme source of drugs and India is endowed with a wide variety of them with high medicinal values. The Quorum Sensing (QS) quenching efficiency of various solvent extracts of Melia dubia seeds was investigated against uropathogenic Escherichia coli (UPEC) to screen the competitive inhibitor of SdiA, a transcriptional activator of quorum sensing in E. coli. In this study, potentiality of five different extracts of Melia dubia seeds for quorum sensing inhibitory activity was investigated against uropathogenic Escherichia coli (UPEC). Assays such as cell density, swarming motility, protein, protease, hemolysis, hemagglutination, hydrophobicity and biofilm inhibition were performed. Biofilm, hemolysis and swarming motility were found to be inhibited by 92.1%, 20.9 % and 48.52% respectively, when the medium was supplemented with 30 mg/ml of the ethanolic extract. GC-MS spectrum of the ethanolic extract showed an array of 27 structurally unlinked compounds with natural ligand C8HSL. The docking against QS transcriptional regulator SdiA was predicted by in silico studies and the ligand C6 showed significant activity with -10.8 GScore. In vitro and in silico docking analysis showed fairly a good correlation, suggesting that the ethanolic extract showed potency to attenuate quorum sensing of uropathogenic E. coli. Further studies by in vitro and in vivo strategies are necessary to foresee the quorum quenching effect of the ligands.

Development of a biofilm inhibitor molecule against multidrug resistant Staphylococcus aureus associated with gestational urinary tract infections

“…The present study involves the screening, synthesis and validation of a potent compound against SarA of S. aureus associated with gestational urinary tract infections, in light of our previous studies that showed potent antibiofilm activity in root ethanolic extract of M. dubia against uropathogenic E. coli (Vinothkannan et al, 2013 ; Adline Princy et al, 2014 ) and antibiofilm activity of SarABI against S. aureus associated with vascular graft infections (Arya et al, 2015 ). In brief, the proposed inhibitor, UTI QQ against SarA protein was computationally validated to have a high affinity toward the target and it was synthesized by a two step process, i.e., reductive amination and steglich esterification for further in vitro and in vivo validation.…”

Resistance to Quorum-Quenching Compounds

“…In addition, five inducers and three inhibitors which are molecularly distant from the native autoinducer N-3-oxododecanoyl-Lhomoserine lactone have been investigated as potential QQ compounds (26). As another example of these modeling approaches, competitive inhibitors of SdiA, a signal receptor of the QS signals of other bacteria in Escherichia coli, have been screened from Melia dubia seed extracts, and 27 compounds structurally unrelated to autoinducers show potential for attenuating QS in uropathogenic E. coli (27). Also, molecular docking was used to identify potential QQ compounds from bark extracts of the mangrove plant Rhizophora annamalayana (28).…”

Plausible Drug Targets in the Streptococcus mutans Quorum Sensing Pathways to Combat Dental Biofilms and Associated Risks

“…The review has highlighted the importance of QS pathway in S.mutans and its role in formation of biofilm along with other virulence properties. Quite a few efforts has been taken to modulate QS to reduce the production of biofilm and associated virulence factors like Hentzer and Givskov, Ravichandran et al, Arya et al, Hema et al, and Wright et al, have described the application of antagonists that act as QS inhibitors to attain the inhibition of virulence genes under QS circuit to prevent the various infections caused by Pseudomonas aeruginosa, Vibrio cholerae and Staphylococcus aureus [28,33,[70][71][72][73][74][75][76]. The approach ensures its success in the fact that, anti-quorum compounds may control virulence traits of pathogenic microbes without significant effects on viability of bacterial cells [77].…”