Investigating the antimicrobial and immunomodulatory effects of honeybee venom peptide apamin in the Drosophila genetic platform

Apamin, an 18-amino acid peptide neurotoxin, constitutes a significant portion of honeybee venom. Although traditionally recognized for its neurotoxic effects, our research demonstrates that apamin exhibits potent antimicrobial properties when genetically expressed in Drosophila . The antimicrobial efficacy of apamin is independent of its disulfide bonds and is enhanced when the peptide is membrane-tethered. This expression selectively targets and inhibits specific harmful bacterial species, such as Pseudomonas aeruginosa , Enterococcus faecalis , and Escherichia coli , while promoting beneficial bacteria like Lactobacillus plantarum thereby improving the gut microbiome. The antimicrobial activity of apamin is localized to the gut and is associated with increased proliferation of intestinal stem cells, acidification of the midgut pH, and activation of enteroendocrine cell calcium signaling. Furthermore, apamin’s antimicrobial function is dependent on specific peptidoglycan recognition proteins, with PGRP-LA and PGRP-SCs being essential. Apamin expression alone is sufficient to restore the integrity of the gut barrier compromised by stressed conditions. Ultimately, apamin supplementation enhances honeybee gut health, particularly in the presence of ingested bacteria. The expression of other honeybee antimicrobial peptides also significantly reduces bacterial infection in flies. Overall, our study provides a comprehensive understanding of the molecular function and regulation of honeybee venom peptides and antimicrobial peptides, utilizing the Drosophila model system to unravel their mechanisms of action and therapeutic potential.