Antimicrobial resistance is increasing globally and is one of the major public health concerns. This highlights the need to search for new antimicrobial agents. Natural fruit by-products are a rich source of bioactive compounds. Pomegranate (Punica granatum) fruit is particularly rich in phenolic bioactive phytochemicals. These compounds are known for their antioxidant, anti-inflammatory, and anticancer properties. Furthermore, they exhibit a broad spectrum of antimicrobial effects. Bioactive phytochemicals are found mainly in peel (exocarp and mesocarp), which constitutes about 50% of the whole fresh fruit. This study utilized pomegranate of Jordanian origin to evaluate the antimicrobial activity of different Pomegranate peel extracts (PPEs) alone and/or in combination with antibacterial agents against four bacterial strains. Different solvents and extraction methods were employed to obtain the PPEs. A key focus was to explore the enhancement of antibacterial activity against gentamicin-resistant Pseudomonas aeruginosa (P. aeruginosa) when microwaved aqueous extracts are combined with gentamicin. The antibacterial activity of PPEs varied depending on the extraction method and the solvent used. Notably, the aqueous macerate and microwave-assisted extract showed high potency and similar activity against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and P. aeruginosa (MICs 12.5, 25, and 25 μg/μL, respectively for both aqueous extracts). In contrast, Proteus mirabilis (P. mirabilis) was more susceptible to the inhibitory activity of organic PPEs with a MIC of 25 μg/μL recorded with the use of ethanolic solvents. Bacterial antagonistic activity was observed against gentamicin-resistant P. aeruginosa, particularly when lower concentrations (3.125, 1.562, 0.781, and 0.39 μg/μL) of microwaved aqueous PPEs were evaluated in combination with different concentrations of gentamicin. In conclusion, pomegranate peels, a natural and safe by-product, demonstrate promising antimicrobial potential. Furthermore, combining PPEs with conventional antibiotics shows promise in addressing antibiotic resistance, highlighting their potential role in treating infectious diseases.
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