Multitarget Inhibition of MRSA Cell-Wall Biosynthesis by Zanthoxylum acanthopodium: Gene Expression, and Molecular Docking for Antibiotic-Resistant Oral Infections
Zanthoxylum acanthopodium; MRSA; murA; mecA; molecular docking; phytochemicals
AuthorsAbstractObjective: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important pathogen in persistent oral infections because of its resistance to β-lactam antibiotics. This study investigated the antibacterial potential of the methanolic fraction of Zanthoxylum acanthopodium against MRSA by evaluating its effects on murA and mecA gene expression and characterizing the molecular interactions of its major phytochemicals with murA and penicillin-binding protein 2a (PBP2a). Methods: The methanolic fraction of Z. acanthopodium fruit, , was tested against MRSA ATCC 33591 at concentrations of 25, 50, and 100 mg/mL. Relative murA and mecA mRNA expression levels were quantified using quantitative real-time PCR and analyzed with the 2^-ΔΔCt method. Statistical analysis used the Shapiro-Wilk and Kruskal-Wallis tests. Molecular docking was conducted using AutoDock 4.2 to evaluate the binding interactions of the identified phytochemicals containing diosmetin, eucalyptol, and gallotannin with murA and PBP2a. Results: The greatest biological suppression of murA and mecA expression occurred at 50 mg/mL, reducing relative expression to .84-fold and .15-fold, respectively, compared with untreated controls. Although the differences among treatment groups were not statistically significant (murA, p = .39; mecA, p = .42), the observed transcriptional trend suggested coordinated inhibition of bacterial cell-wall biosynthesis and methicillin resistance pathways. Molecular docking showed that diosmetin had the most favorable interactions with both murA and PBP2a, while eucalyptol and gallotannin also formed stable non-covalent interactions with both target proteins, which supports a multitarget antibacterial mechanism. Conclusion: The methanolic fraction of Z. acanthopodium exhibits promising anti-MRSA activity through simultaneous modulation of murA and mecA and predicted interactions with murA and PBP2a. These findings indicate Z. acanthopodium as a potential source of adjunctive phytotherapeutic agents for managing antibiotic-resistant oral infections. Further functional, pharmacological, and clinical studies are needed to validate its translational application in evidence-based dental practice.
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