Resveratrol, quercetin, and epigallocatechin gallate (EGCG) were computationally screened against LuxS — a key enzyme in the autoinducer-2 (AI-2) quorum sensing pathway of multidrug-resistant Klebsiella pneumoniae. Despite quercetin (ΔG = −45.47 kcal/mol) and EGCG (−43.04 kcal/mol) showing stronger predicted binding affinities, resveratrol's superior molecular dynamics stability (RMSD: 1.8 ± 0.2 Å) and persistent contacts with residues Tyr63 and Trp68 translated into better experimental performance. At 32 µg/mL (MIC/MBC), resveratrol significantly suppressed quorum sensing phenotypes and reduced dual-species Klebsiella–Acinetobacter baumannii biofilm by 54.7%.
This finding matters because it reframes a familiar nutraceutical — resveratrol, long studied for SIRT1 activation and cardiovascular benefit — as a potential anti-virulence scaffold against one of WHO's critical-priority pathogens. Crucially, the target here is not bacterial killing per se but quorum sensing disruption, a strategy that theoretically imposes lower selective pressure for resistance development compared to conventional antibiotics. The Klebsiella–Acinetobacter dual-species biofilm model adds clinical realism, since co-infections with these organisms are increasingly documented in ICU settings. Limitations are significant: these are in vitro results with no pharmacokinetic data, and resveratrol's notoriously poor oral bioavailability (~1%) raises serious questions about achievable tissue concentrations at 32 µg/mL. The study is best read as hypothesis-generating — identifying LuxS as a druggable target and resveratrol's scaffold as worth optimizing — rather than a near-clinical breakthrough.
