Multifaceted antibacterial effects of Pistacia chinensis extract against methicillin-resistant Staphylococcus aureus through membrane disruption, ROS reduction, and β-lactamase inhibition

AIM: Methicillin-resistant Staphylococcus aureus (MRSA), a major pathogen associated with severe infections, poses a significant challenge to antimicrobial resistance (AMR) management. This study investigates the antibacterial activity of Pistacia chinensis (PciE) (commonly known as Kakdashringi in traditional Indian medicine) against MRSA and explores its mechanisms of action in resistance modulation, underscoring its potential therapeutic applications. METHODS AND RESULTS: The antibacterial efficacy of PciE was assessed using disc diffusion, MIC determination, FESEM imaging, and assays for ROS generation, K⁺ efflux, and blaTEM gene expression. PciE demonstrated a dose-dependent inhibitory effect on MRSA strains, with MIC values ranging from 0.65 to 0.83 mg/ml. FESEM revealed membrane disruption and morphological changes in PciE-treated MRSA cells. PciE reduced ROS levels, mitigated blaTEM expression, and protected methicillin from β-lactamase degradation. Co-treatment with PciE and methicillin restored drug susceptibility in MRSA. Importantly, PciE showed low resistance induction over 15 days and significantly inhibited bacterial invasion into human keratinocytes, with no cytotoxic effects at therapeutic concentrations. CONCLUSIONS: PciE exhibits potent antibacterial activity against MRSA by targeting membrane integrity, reducing oxidative stress, and interfering with resistance mechanisms. Its combination with methicillin enhances efficacy, offering a promising strategy for combating antibiotic-resistant MRSA infections. While these MIC values are relatively high, the extract's synergistic effect with methicillin and low resistance induction suggest potential topical or adjuvant applications.