Quorum quenching of virulence traits expression in human and plant pathogens by Isoxazolone and its molecular docking studies

Inhibiting quorum sensing (QS) to hinder extracellular polymeric substances (EPS) production and biofilm formation in pathogenic bacteria was studied as an efficient alternative for controlling the infections caused by multiple drug resistant (MDR) bacteria. In the present study, the isoxazolone derivative (4-(2-hydroxy-5-methoxybenzylidene)-3-methylisoxazol-5(4H)-one) was tested for its ability to inhibit EPS production and biofilm formation in human as well as plant pathogenic bacteria. The binding affinity of the derivative to the quorum sensing regulatory proteins (AgrA and LasR) was investigated by carrying out molecular docking studies. The derivative was capable of substantially inhibiting EPS production and biofilm formation in Pseudomonas aeruginosa, Staphylococcus aureus, Erwinia carotovora, and Ralstonia solanacearum at subinhibitory concentrations. Furthermore, molecular docking studies confirmed our results with notable binding affinity –7.5 kcal/mol to transcriptional activator protein LasR and binding affinity –6.8 kcal/mol to AgrA (transcription factor), both controlling expression of virulence factors in P. aeruginosa and S. aureus, respectively. This is a first report that proves that isoxazolone derivatives have quorum quenching potential (QQ) against both human and plant pathogens, which can be applied in medical and agricultural fields.