Synergistic Effects of Antimicrobial Peptide Dendrocin‑ZM1 Combined with Conventional Antibiotics Against Methicillin-Resistant Staphylococcus aureus

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is the most prevalent type of bacterial resistance. Consequently, it is crucial to develop novel treatments to address bacterial resistance. Objectives: Dendrocin-ZM1 (DZM1) and vancomycin are two compounds whose effects on MRSA are examined in this study. Methods: The synergistic bactericidal effect of the peptide-conventional antibiotic combinations was evaluated using the minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC) assays, and checkerboard method. Additionally, the time-killing kinetics of DZM1 alone and in combination with vancomycin on MRSA ATCC 43300 strain were assessed. Structural alterations and morphological changes of the MRSA ATCC 43300 strain exposed to DZM1 (1/16 MBC) and vancomycin (1/8 MBC), alone or in combination (1/16 MBC DZM1 + 1/8 MBC vancomycin), were analyzed using transmission electron microscopy (TEM) and scanning electron microscopy (SEM), respectively. Results: Dendrocin-ZM1 exhibited antimicrobial activity against MRSA clinical isolates and MRSA ATCC 43300 (MIC and MBC: 16 μg/mL). A synergistic effect was observed when DZM1 was combined with vancomycin (FIC: 0.187) against MRSA ATCC 43300. The combination of DZM1 with vancomycin at sub-MBC concentrations demonstrated sustained bactericidal activity against MRSA ATCC 43300 strain. According to SEM results, DZM1 increased bacterial cell membrane permeability, enhancing the antibacterial activity of vancomycin. Transmission electron microscopy analysis revealed severe membrane damage and subsequent cell lysis in the MRSA ATCC 43300 strain when treated with the combination of DZM1 and vancomycin. Conclusions: This study supports the potential use of these compounds to reduce reliance on conventional antibiotics and highlights their promise as alternatives for combating bacterial resistance.