Peptide PN5 from Pinus densiflora 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 Pinus densiflora 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 S. Typhimurium 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 S. Typhimurium 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.