Drug Repurposing and Synergistic Potential with Epigallocatechin Gallate Nanocomposite: A Novel Alternative Therapeutics Against Pseudomonas aeruginosa

Pseudomonasaeruginosa is a frequent and virulent microbiological species that causes hospital-acquired illness, wound infection, and wound healing mechanism impairment. P. aeruginosa exhibits antibiotic resistance, placing it in the category of antibiotic-resistant bacteria for which alternate inhibitory drugs are urgently needed. In light of the antibacterial efficacy of green tea and the repurposing of antibiotics to overcome antibiotic resistance, the current study emphasizes the effectiveness of green tea epigallocatechin gallate (EGCG)-encapsulated metal-based nanocomposite hydrogel and examines its inhibitory potential in combination with selected antibiotic against P. aeruginosa. In silico investigation was done to identify a potential novel antibacterial compound against PvdF protein, which aids in siderophore-pyoverdin biosynthesis in P. aeruginosa. Further, the candidate with the most significant molecular interaction with PvdF protein was evaluated for synergistic antibacterial effect in combination with the EGCG nanocomposite hydrogel using in vitro studies. EGCG-encapsulated silver nanoparticles (EGCG-AgNPs) were prepared using the chemical reduction method. The size and zeta potential of nanoparticles were estimated using a particle size analyzer and were depicted to be 185.1 nm and - 20.6 mV respectively. The EGCG-AgNPs were characterized by a UV-Vis spectrophotometer, and the absorbance was recorded in the range of 296 to 275 nm. The FTIR spectroscopy revealed peaks near 3972.30 cm(-1), 3187.40 cm(-1), and 726.31 cm(-1) attributed to OH, -CH, and CO functional groups and contributing to the antibacterial efficacy of EGCG-AgNPs. SEM-EDX analysis depicted that the synthesized EGCG-AgNPs were crystalline and quasi-spherical in shape with a size range of 180-200 nm. Furthermore, the hydrogel of nanocomposite was prepared using flex seed gum, and its physical characterization was performed. The EGCG-AgNPs hydrogel was assessed for its synergistic antibacterial potential against P. aeruginosa, using the broth microdilution method and FIC (fractional inhibitory concentration) assay, indicating the synergistic inhibitory effect from 98.81 +/- 0.14 to 72.80 +/- 0.15% (P < 0.5) respectively. The present study demonstrated a novel candidate for drug repurposing and therapeutic strategy that has the potential to produce a safer nano-herbal synergistic antibacterial formulation against P. aeruginosa. Further mechanistic insight into the inhibitory potential of the EGCG nanocomposite hydrogel is required to be investigated in the future.