Peptide PN5 from <i>Pinus densiflora</i> Confers in Vivo Protection Against Multidrug-Resistant Salmonella Typhimurium Through Membrane Disruption

Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics. In the present study, we investigated PN5, an AMP derived from <i>Pinus densiflora</i> needles, as a potential anti-infective agent against multidrug-resistant (MDR) Salmonella Typhimurium. PN5 exhibited potent antibacterial activity without cytotoxicity, retained stability across diverse pH and temperature conditions, inhibited biofilm formation, and disrupted bacterial membranes. It eliminated intracellular <i>S. Typhimurium</i> in infected RAW 264.7 macrophages, reducing bacterial survival and promoting clearance. Mechanistically, PN5 modulated host immunity by regulating NF-κB and MAPK signaling. In a murine <i>S. Typhimurium</i> infection model, PN5 significantly improved survival by enhancing bacterial clearance and suppressing pro-inflammatory cytokines. These findings establish PN5 as a dual-function antimicrobial agent combining direct bactericidal activity with immune modulation, providing therapeutic potential against MDR bacterial infections.