Assessment of Polyherbal Extract as Potential Inhibitor of Penicillin Binding Proteins in Drug Resistant Escherichia coli Using Computational and Experimental Approach

[摘要] ObjectivesThe emergence of multidrug-resistant Escherichia coli (MDR E. coli), especially in the nosocomial environment, has increased the need to find alternative therapeutics. This study aims to explore the antibacterial properties of a polyherbal ethanolic extract of Ricinus communis, Emblica officinalis, Terminalia bellerica, Terminalia chebula, Zingiber officinale, Curcuma longa and Boswellia serrata against MDR and extensively drug-resistant (XDR) E. coli.MethodsChromatographic analysis of polyherbal extract was performed by LC-MS/MS. Disc diffusion and MIC assays were performed to assess susceptibility of resistant E. coli clinical isolates and to measure the antibacterial activity of polyherbal extract; the resistance profiling was compared between meropenem and the polyherbal extract. The polymerase chain reaction was used to detect prevalent resistance gene (blaNDM and blaOXA) in E. coli clinical isolates. Molecular docking of PBP1b, PBP2, PBP3 and β-lactamase evaluated the binding affinities of major phytoconstituents. For ADMET screening the SwissADME and Protox were used.ResultsThe optimized C18 gradient method showed good consistency and sharp peak resolution. The molecular weights of phytocompounds ranged from 270.24 to 610.52 g/mol and LogP values were ≤ 5 while all, except rutin, fulfilled Lipinski’s rule of five. Predicted LD50 values ranged from 159–10000 mg/kg, with most toxicity classes 4–5 and minor alerts for some analogs for quercetin, which had a higher toxicity (class 3). Disc diffusion method and MIC determination in vitro tests showed inhibitory activity with MIC ranging from 1560 to 6250 µg/mL. The mean MIC value of meropenem and polyherbal extract was 178.4 µg/mL and >1000 ug/mL respectively, the polyherbal extract showed uniform efficacy. The resistance genes blaNDM 1(35%and blaOXA 48(31%) are detected in all isolates using PCR method. Molecular docking of the main resistance-associated targets such as PBP1b, PBP2, PBP3, and β-lactamase have demonstrated that the phytoconstituents, including apigenin-7-O-glucoside, ellagic acid, galangin, and cyclocurcumin, possessed a high binding affinity with strong interaction at the active site when compared to meropenem highlighting the need of further experimental validation.ConclusionThe overall outcome of the computational and experimental results suggests the polyherbal extract as a potential candidate offering new therapeutics to be used against resistant E. coli strains.

[发布日期] 2026-08-01

[关键词] Escherichia coli;polyherbal extract;molecular docking;MDR/XDR;penicillin binding proteins