%A Suman Paul
%A Argajit Sarkar
%A Manisha Ghosh
%A Debajyoti Datta
%A Moumita Debnath
%A Surajit Basak
%A Saumya Raychaudhuri
%A Surajit Bhattacharjee
%J 3 Biotech
%T Quercetin as an additive adjuvant enhances ciprofloxacin and tetracycline efficacy against Vibrio cholerae by disrupting membranes, inhibiting biofilms, and reducing virulence levels
%X Quercetin (QR), a plant-derived flavonoid, was evaluated as an adjuvant to enhance ciprofloxacin (CP) and tetracycline (TE) efficacy against Vibrio cholerae O1 El Tor (C6706) and non-O1/non-O139 (SC134) strains. Checkerboard assays revealed additive effects (FICI = 0.75) for QR+CP and QR+TE against both strains, with synergy (FICI = 0.5) for QR+TE in C6706. QR-antibiotic combinations significantly increased membrane permeability (by 162-188% in C6706 and 151-189% in SC134) and intracellular reactive oxygen species (ROS) generation (by 229-262% in C6706 and 211-241% in SC134), potentiating antibiotic-induced bacterial death. Sub-MIC combinations markedly inhibited biofilm formation (67-76%) and reduced viable biofilm cells (CFU counts), supported by crystal violet (CV) and FESEM imaging. QR and antibiotics at higher doses (multiple MICs) eradicated preformed biofilms (77-79% in C6706; 40-43% in SC134). Quantitative assays confirmed significant reductions in biofilm matrix components, exopolysaccharides (73-82%), proteins (59-67%), and extracellular DNA (79-92%). QR also decreased cell surface hydrophobicity, induced morphological elongation, and impaired adhesion. Furthermore, QR combinations significantly suppressed swimming motility and protease activity, indicating attenuation of virulence. In silico docking showed strong binding of QR-antibiotic complexes to key regulatory proteins governing biofilm (VpsR, RbmA, Bap1), virulence (LuxO, AphA), and morphology (CrvA), suggesting targeted pathway interference. Collectively, these findings demonstrate that QR enhances the antibacterial, antibiofilm, and antivirulence efficacy of CP and TE against V. cholerae through multi-mechanistic modulation of membrane permeability, oxidative stress, and virulence regulation, supporting its potential as an effective antibiotic adjuvant. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-025-04621-x.
%N 1
%P 3
%V 16
%D 2025
%I Springer Science and Business Media LLC
%L open3254