Phytochemical Characterization of Schinus terebinthifolia Leaf Phytobiotics and Their Potential as Natural Antibiotic Adjuvants Against Carbapenem-Resistant Bacteria

Abstract

The emergence of carbapenem-resistant Gram-negative bacteria has intensified the search for natural compounds capable of restoring antibiotic efficacy by targeting β-lactamase-mediated resistance. This study investigated the antibacterial, β-lactamase inhibitory, and in silico potential of Schinus terebinthifolia leaf phytobiotics. Soxhlet (STS), maceration (STM), and essential oil (STEOL) extracts were evaluated against carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa using agar diffusion, broth microdilution, checkerboard, and colorimetric β-lactamase inhibition assays. In parallel, the phytochemicals identified by GC–MS and LC–MS were virtually screened against the VIM and OXA-48-like β-lactamases using PyRx, followed by drug-likeness prediction using SwissADME. All phytobiotics exhibited significant antibacterial activity and synergistically enhanced the efficacy of cefotaxime against the majority of the tested bacterial strains (ΣFICI ≤ 0.5). Moreover, they markedly inhibited β-lactamase activity, with complete inhibition achieved at MIC/2. Among the tested phytobiotics, STS exhibited the greatest β-lactamase inhibitory potency, with an IC50 of 49.8 μg/mL. Virtual screening identified diosmetin, catechin, quercetin, ellagic acid, and epicatechin gallate as the most promising candidate β-lactamase inhibitors, exhibiting strong binding affinities toward VIM and OXA-48-like β-lactamases. SwissADME analysis further indicated favorable drug-like properties for the top-ranked compounds. Collectively, these findings suggest that S. terebinthifolia phytobiotics have promising antibacterial and β-lactamase-inhibitory potential and may represent a source of candidate compounds for further investigation as antibiotic adjuvants against carbapenem-resistant Gram-negative pathogens.