Anti-quorum sensing effects of batatasin III: in vitro and in silico studies

Abstract

The spread of multidrug resistant bacteria has fueled the development of new antibiotics to combat bacterial infections. Disrupting the quorum sensing (QS) mechanism with biomolecules is a promising approach against bacterial infections. Plants used in Traditional Chinese Medicine (TCM) represent a valuable resource for the identification of QS inhibitors. In this study, the in vitro anti-QS activity of 50 TCM-derived phytochemicals against the biosensor Chromobacterium violaceum CV026 was tested. Among the 50 phytochemicals, 7-methoxycoumarin, flavone, batatasin III, resveratrol, psoralen, isopsoralen, and rhein inhibited violacein production and showed good QS inhibitory effects. Batatasin III was selected as the best QS inhibitor based on drug-likeness, physicochemical properties, toxicity, and bioactivity score prediction analyses using SwissADME, PreADMET, ProtoxII, and Molinspiration. At 30 μg/ mL, Batatasin III inhibited violacein production and biofilm formation in C. violaceum CV026 by more than 69% and 54% respectively without affecting bacterial growth. The in vitro cytotoxicity evaluation by MTT assay demonstrated that batatasin III reduced the viability of 3T3 mouse fibroblast cells to 60% at 100 μg/mL. Furthermore, molecular docking studies showed that batatasin III has strong binding interactions with the QS-associated proteins CViR, LasR, RhlR, PqsE, and PqsR. Molecular dynamic simulation studies showed that batatasin III has strong binding interactions with 3QP1, a structural variant of CViR protein. The binding free energy value of batatasin III-3QP1 complex was −146.295 ± 10.800 KJ/mol. Overall results suggested that batatasin III could serve as a lead molecule that could be developed into a potent QS inhibitor. Communicated by Ramaswamy H. Sarma