Abstract
Antimicrobial peptide BmKn2-7, a rationally optimized derivative of the scorpion venom peptide BmKn2, shows strong potential as an antibiotic alternative for controlling Vibrio parahaemolyticus in aquaculture. This study evaluated its antibacterial mechanisms and in vivo efficacy in Litopenaeus vannamei through biochemical assays, transcriptomic profiling, and challenge experiments. BmKn2-7 exhibited potent in-vitro activity (MIC = 125 µg/mL) and disrupted bacterial homeostasis by increasing membrane permeability, inducing oxidative stress, and inhibiting P-type ATPase. RNA-seq analysis revealed extensive transcriptional reprogramming, including the downregulation of quorum-sensing, virulence, and β-lactam resistance–associated genes. In vivo, BmKn2-7 significantly improved shrimp survival following V. parahaemolyticus infection and selectively reduced Vibrio abundance in the gut without compromising overall microbiota diversity. Together, these findings demonstrate that BmKn2-7 acts through complementary bactericidal and anti-virulence pathways while promoting intestinal microbial resilience, supporting its potential as a promising antimicrobial candidate for reducing vibriosis risk in shrimp aquaculture. Supplementary Information: The online version contains supplementary material available at 10.1186/s12917-025-05264-z.