Novel Anti-MRSA Peptide from Mangrove-Derived FN33 Supported by Genomics and Molecular Dynamics.

Antimicrobial resistance (AMR) is a global health threat, with methicillin-resistant (MRSA) being one of the major resistant pathogens. This study reports the isolation of a novel mangrove-derived bacterium, FN33, as identified through genome analysis and the discovery of a new anionic antimicrobial peptide (AMP) exhibiting anti-MRSA activity. The AMP was composed of 23 amino acids, which were elucidated as NH-Glu-Gly-Gly-Cys-Gly-Val-Asp-Thr-Trp-Gly-Cys-Leu-Thr-Pro-Cys-His-Cys-Asp-Leu-Phe-Cys-Thr-Thr-COOH. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for MRSA were 8 µg/mL and 16 µg/mL, respectively. FN33 AMP induced cell membrane permeabilization, suggesting a membrane-disrupting mechanism. The AMP remained stable at 30-40 °C but lost activity at higher temperatures and following exposure to proteases, surfactants, and extreme pH. All-atom molecular dynamics simulations showed that the AMP adopts a β-sheet structure upon membrane interaction. These findings suggest that FN33 is a promising source of novel antibacterial agents against MRSA, supporting alternative strategies for drug-resistant infections.