Galangin synergistically revives the antibacterial activity of vancomycin against vancomycin-resistant Enterococcus faecium

Enterococcus faecium is one of the most important opportunistic pathogens threatening human health worldwide. Resistance to vancomycin (VAN) is increasing at an alarming rate. Resurrecting antibiotics using a combination approach is a promising alternative avenue. Galangin (GAL) is a bioactive compound constituted in herbal plants. This study aimed to evaluate the synergistic activity of the combination of GAL and VAN and mode of action against vancomycin-resistant E. faecium (VREfm) strains. The minimal inhibitory concentrations against these bacteria were 8-64 μg ml-1 for VAN and 512 μg ml-1 for GAL. The VAN plus GAL combination exhibited synergistic effects against E. faecium isolates, with a fraction inhibitory concentration index of 0.26-0.28. Time-kill assays confirmed this synergism. Mechanistic studies showed that the combination induced intracellular constituent leakage, suggesting impaired membrane permeability and electron microscopy revealed peptidoglycan and membrane damage. Additionally, the GAL plus VAN combination inhibited biofilm formation and significantly reduced lipid, protein, and carbohydrate contents, as shown by Fourier-transform infrared spectroscopy (FTIR). GAL could reverse the activity of VAN against VREfm by damaging bacterial cell envelope, inhibiting biofilm formation, and reducing biomolecule contents, emphasizing its potential as a valuable adjunct to VAN in treating VREfm infections.