Chemical profiling and mechanistic insights into the antibacterial efficacy of Melaleuca cajuputi leaf extract.

Abstract

Background: The emergence of antimicrobial resistance and the prevalence of bacterial infections have prompted the search for novel antimicrobials with diverse therapeutic potential from natural products. Thus, this study investigated the antibacterial efficacy of the leaf extracts of M. cajuputi. Additionally, the chemical composition and the mechanism of action of the most active extract (MAE) were evaluated.

Methods: The antibacterial activity of leaf extracts of M. cajuputi was assessed using the broth microdilution assay. Scanning electron microscopy (SEM) was used to investigate the effects of MAE on the morphology of bacterial cells. Meanwhile, the chemical composition of the MAE was analyzed using Fourier transform infrared (FTIR) spectroscopy and gas chromatography-mass spectrometry (GC-MS). AutoDock Vina was used for molecular docking analysis to unveil the interactions between the ligands and the active sites of the target bacterial proteins.

Results: The crude extracts were obtained through cold maceration. The methanolic extract demonstrated the most significant antibacterial activity, with minimum inhibitory concentration (MIC) values spanning 0.25 mg/mL to 2 mg/mL. After 12 h of treatment with 1 × MIC of the methanolic extract, the bacteria showed discernible morphological alterations, including disrupted cell wall and membrane integrity. Thirty compounds were identified in the MAE and subsequently subjected to molecular docking studies against target bacterial proteins. Amongst the compounds, methylanthracene, cycloisolongifolene, diphenyl imidazole, benzil monohydrazone, and trimethoxybenzoic acid showed pronounced binding affinities towards Klebsiella pneumoniae membrane protein (PDB ID: 5O79), peptide binding protein (PDB ID: 7RJJ), Streptococcus agalactiae cell wall surface anchor (PDB ID: 2XTL), pilin (PDB ID: 3PHS), Staphylococcus aureus transglycosylase (PDB ID: 3VMQ), and penicillin-binding proteins (PDB ID: 3VSK). The binding energy scores for these interactions varied between - 6.0 kcal/mol and - 7.5 kcal/mol. Molecular dynamics simulations validated the stability of these interactions, reinforcing the in vitro findings of cell wall and membrane disruption​.

Conclusion: The findings of this study indicated that the methanolic extract of M. cajuputi leaves displayed potent antibacterial activity against Klebsiella pneumoniae, S. agalactiae, and S. aureus. The molecular docking analysis reveals significant binding interactions between the identified compounds and the target bacterial proteins, highlighting the potential of M. cajuputi as a novel source of anti-infectives targeting bacterial infections.