Exploring a new phyto-derived nanoparticle for targeting bacterial protein EF-Tu: an integrated approach to develop antimicrobial drug

Abstract

ABSTRACT The application of antibiotic medicine to save numerous lives is in jeopardy due to the alarming elevation in antibiotic-resistant organisms as a consequence of improper and imprudent usage of antibiotics. This study investigated the antibacterial efficacy of pelargonidin (PG) by employing a cost-effective nano-formulation-based targeted drug delivery system as an alternative to conventional strategies. The precise targeting of bacteria was made easier by synthesizing nano-particles of phyto-product pelargonidin (NPG) by employing poly-lactide-co-glycolide (PLGA), a biodegradable polymer. The physico-chemical characterization of NPGs was performed via AFM study and the antibacterial efficacy of NPGs tested against Escherichia coli and Staphylococcus aureus was assessed by agar disc diffusion method. Additionally, the docking platform explored in this study enabled the prediction of the ability of PG to occupy the binding pocket of EF-Tu (elongation factor thermo unstable), a vital bacterial protein that operates on a translational level. The overall results implicate that NPG was an effective drug candidate against the gram-negative bacteria E. coli and the gram-positive bacteria S. aureus according to the diameter of the inhibition zone (23 ± 0.82 mm: E. coli and 22.67 ± 1.25 mm: S. aureus). Furthermore, in silico analysis revealed that the NPG-EF-Tu complex had an excellent docking score of −9.13 Kcal/mol, indicating key amino acid residues required for interaction, and anticipating the signaling component/s involved that may be hindered by NPG, thereby leading to a decline of bacterial growth. The core phyto-compound of NPG (pelargonidin) could effectively bind to EF-Tu thereby exercising strong antimicrobial efficacy against both E. coli and S. aureus making it a potential alternative to the usage of commercial antibacterials with a history of drug-resistance.