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

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.

GRAPHICAL ABSTRACT

KEYWORDS:

• Antimicrobial resistance
• molecular docking
• nanoformulation
• pelargonidin
• Staphylococcus aureus
• Escherichia coli

Acknowledgments

The authors would greatly acknowledge UGC, New Delhi for the UGC-BSR (Grant no: F.30-488/2019(BSR) sanctioned to Dr. Asmita Samadder for this research work. The authors would also like to acknowledge University of Kalyani for providing Personal Research Grant to AS and SHM which was used for the research work. R. D. and S. S. are thankful to UGC for their SRF fellowship. Authors would also like to acknowledge Dr. Debojyoti Tarafdar, Assistant Professor and Head, Department of Chemistry, Chanchal College for interpreting the FTIR data. Authors are sincerely thankful to their corresponding institutes for providing necessary research facilities.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors would greatly acknowledge UGC, New Delhi for the UGC-BSR (Grant no: F.30-488/2019(BSR) and SERB (DST) (Grant No.:ECR/2017/000355/LS) for providing research grant sanctioned to Dr. Asmita Samadder to carry out this research work.