P. gingivalis is a significant pathogen in periodontal disease, a chronic inflammatory condition disturbing tooth-supporting tissue. Its systemic distribution has been linked to cardiovascular disease, rheumatoid arthritis, and Alzheimer’s disease. This study aimed to design and evaluate a novel antimicrobial peptide targeting P. gingivalis.

The active site of bacteriocin nisin was first identified through bioinformatics analysis and subsequently enhanced structurally by adding arginine at the N-terminus. The antimicrobial properties, stability and toxicity of the modified peptide were investigated using in silico tools (AMPA, AMP Scanner, sAMPpred-GAT). In vitro assays measured its effects on P. gingivalis growth (OD600), viability (CFU/mL) and biofilm formation at concentrations from 4–128 µg/mL.

Computational analysis indicated the antimicrobial potency, structural resilience, and mammalian cell safety of this peptide. In vitro evaluation showed dose-dependent inhibition of P. gingivalis growth (MIC: 32 µg/mL), bactericidal activity (MBC: 128 µg/mL), and meaningful biofilm reduction (64 µg/mL).

The engineered peptide holds promising efficacy against P. gingivalis, supporting AMPs as potential therapeutics for periodontal and systemic P. gingivalis-associated conditions. Further mechanistic and preclinical studies are warranted.