Antimicrobial peptide YAMP1 derived from Lactiplantibacillus plantarum: A Safe Candidate to Combat Toxoplasma gondii Infection

T. gondii is a foodborne zoonotic parasitic protozoa that can infect all warm-blooded animals, including humans. There are currently no widely applicable vaccines or specific drugs. Clinical treatment primarily relies on antibiotics, which exhibit limited efficacy and carry certain toxic and side effects. LAB-derived AMPs offer high safety and low propensity for inducing resistance. Based on the identification of peptides from L. plantarum -derived AMPs Y8-2, followed by the synthesis and screen, the antimicrobial peptide used in this study, designated YAMP1, was obtained. Its amino acid sequence is QGHLNSPTTVNRSLNALR and has a killing rate of 85.74% on tachyzoites ( P < 0.0001). YAMP1 can specifically target and destroy the SAG1 protein on the surface of tachyzoite cells, causing the leakage of cell contents. After oral gavage administration to BALB/c mice, it was found that YAMP1 could alleviated the intestinal inflammation and reduced parasite burden in various tissues and organs on 10 dpi. Furthermore, it mitigated brain inflammation and significantly decreases the number of brain tissue cysts (60.7%, P < 0.001). In addition, YAMP1 could significantly reduce the abundance of Escherichia after T. gondii infection and increase the Akkermansia and Lactobacillus . Metabolomics analysis demonstrated that YAMP1 significantly influenced metabolic changes, with notable enrichment in pathways including primary bile acid metabolism and tryptophan metabolism, contributing to the mitigation of T. gondii infection. Our study expands new avenues for exploring potential alternative treatments for T. gondii infection. In addition, it provides data supporting the use of LAB-derived AMPs for treating toxoplasmosis and broadens the prospects for the development and utilization of LAB-derived AMPs.