Unveiling the potential antibacterial mechanism of Melaleuca cajuputi leaf extract by cell morphology studies and molecular docking analysis

Abstract

The antimicrobial properties of the Melaleuca cajuputi plant have been documented. However, the underlying antimicrobial mechanisms remain relatively unexplored. Thus, this study aimed to investigate the antibacterial effects of M. cajuputi leaf extract against selected bacterial strains and unveil the potential antibacterial mechanisms of the most potent sub-fraction through time-kill assay, cell morphology studies, and molecular docking analysis. The fractions and sub-fractions were obtained from the methanolic extract of M. cajuputi leaf by bioassay-guided fractionation. The antibacterial activity was tested against Staphylococcus aureus, Streptococcus agalactiae, Klebsiella pneumoniae, and Escherichia coli using broth microdilution assay. The most potent sub-fraction, Melaleuca fraction 2d (MF2d), demonstrated remarkable antibacterial activity with MIC values ranging from 0.063 to 0.25 mg/mL and induced significant cellular damage against the tested bacteria. The chemical characterization of the most potent sub-fraction (MF2d) from methanolic extract of M. cajuputi leaf identified five (5) compounds with 2-isopropyl-10-methyl phenanthrene (83.09%) as the major component. In-silico molecular docking analysis revealed that all the docked ligands showed strong binding propensity towards target bacterial proteins, including DNA gyrase (PDB ID: 1ZI0), dihydropteroate synthase (PDB ID: 1AD1), and D-alanyl transferase (PDB ID: 6O93) with the binding energy ranging from − 6.0 to − 8.4 kcal/mol. The overall findings demonstrated the potential of the M. cajuputi plant as a valuable source of novel antibacterial agents.