DOI: 10.1177/1934578x261476821 ISSN: 1934-578X
Assessment of Polyherbal Extract as Potential Inhibitor of Penicillin Binding Proteins in Drug Resistant
Escherichia coli
Using Computational and Experimental Approach
Farah Saeed, Mehwish Rizvi, Sabahat Naeem, Rabia Bushra, Rahila Bano, Hina Saleem
Objectives
The 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
.
Methods
Chromatographic 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 (
bla
NDM
and
bla
OXA
)
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.
Results
The 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 LD
50
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
bla
NDM 1
(35%and
bla
OXA 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.
Conclusion
The 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.