Antibacterial Mechanism of a Novel Peptide Dendrocin‑ZM1 Against Staphylococcus aureus by Increasing Membrane Permeability

Staphylococcus aureus is a prevalent pathogen responsible for healthcare and community-acquired infections, which lead to elevated rates of fatality and morbidity. With the emergence of bacterial strains that are resistant to multiple drugs, antimicrobial peptides are increasingly recognized as a promising alternative to antibiotics due to their distinctive mode of action and other notable attributes. In our previous investigation, we isolated and characterized an antibacterial peptide from Zataria multiflora Boiss , known as Dendrocin-ZM1, which exhibits potent antibacterial properties against a diverse range of bacterial strains. In this study, we aimed to investigate the anti-staphylococcal mode of action of Dendrocin-ZM1. We examined the interactions of the peptide with the cytoplasmic membrane using DiSC (3)-5, NPN, and PI dyes. Additionally, we analyzed the release of ATP, DNA/RNA from cells exposed to the peptide. Our findings revealed that Dendrocin-ZM1 can eliminate 99.9% of bacteria within 60 min. Furthermore, this peptide demonstrated good stability in the presence of physiological concentrations of salts. Through bactericidal mechanism analysis, we discovered that Dendrocin-ZM1 has the ability to disrupt the integrity of the bacterial membrane, increase its permeability, and cause leakage of cellular content, resulting in membrane damage. Observation of the treated bacteria using transmission electron microscopy (TEM) provided evidence of damage to the cell membrane and subsequent cell lysis. Based on these results, we conclude that Dendrocin-ZM1 shows promising prospects as a new antimicrobial agent.