Structure-based virtual screening for plant-derived SdiA-selective ligands as potential antivirulent agents against uropathogenic Escherichia coli

The uropathogenic Escherichia coli pathogenecity is affected by quorum sensing transcriptional regulator SdiA. In this study, in vitro characterization of the active principles that could potentially antagonize with SdiA from the Melia dubia bark extracts has been described. After in vitro assays carried out to evaluate the inhibitory activities against the uropathogenic E. coli, the ethanolic extract (30 mg/ml) which showed the strongest suppression of haemolysis, swarming motility, hydrophobicity and biofilm formation, was subjected to GC–MS analysis and an array of 40 unrelated compounds was identified. Docking studies was conducted to screen for plant-based SdiA inhibitors. Five hits were assessed for their binding profiles and 7-(1-bromoethyl)-3, 3-dimethyl-bicyclo [4.1.0]heptan-2-one showed 66.95% binding ability with respect to C8HSL.

The interaction between SdiA, a transcriptional regulator of Escherichia coli quorum sensing, and the ligand derived from Melia dubia bark (BL39R1) shows the maximum binding potential.Figure optionsDownload as PowerPoint slideHighlights
► Screened for quorum quenching agents from Melia dubia, against Uropathogenic Escherichia coli.
► BL39R1 as a potential quorum quenching agent with best binding affinity with SdiA.
► A new strategy proposed for the treatment of Uropathogenic E. coli infections.