Pomegranate peel extract as a promising tyrosyl-tRNA synthetase inhibitor of Staphylococcus aureus: in vitro and in silico approach.

Staphylococcus aureus, a common foodborne pathogen, thrives in various environments, including milk, meat, and vegetables. With increasing consumer concerns about the harmful effects of chemical additives, alternative antimicrobial agents are urgently needed. This study evaluates the potential of pomegranate peel extract (PPE) as an inhibitor of the bacterial enzyme tyrosyl-tRNA synthetase (TyrRS). PPE, rich in bioactive compounds such as ellagitannins, ellagic acid, and gallic acid, was extracted using hot water, microwave, and ultrasound methods. The ultrasound assisted extract showed the highest phenol content (178.6 ± 0.6 GAE/g) and antioxidant activity (9.43 ± 1.6 µmole TE/g DW). The MIC value of this extract was found to be 2.0 mg/ml and it inhibited S. aureus growth significantly (20.6 ± 0.31 mm) in agar diffusion tests. To elucidate the molecular mechanism, in silico analyses including molecular docking, molecular dynamics simulations, and MM-PBSA calculations were performed for major PPE-derived phytochemicals, gallic acid, ellagic acid, punicalagin, and punicalin, along with the reference TyrRS inhibitor SB-219,383. Among the tested compounds, punicalagin exhibited the most favorable binding affinity and dynamic stability, with binding free energy comparable to SB-219,383. These findings highlight PPE's potential in combating S. aureus along with utilization of agricultural by-products as source of antimicrobial substance that has the potential of offering a sustainable approach to antimicrobial resistance.