Investigating the immunomodulatory effects of honeybee venom peptide apamin in Drosophila platforms.

Apamin, an 18-amino-acid honeybee venom peptide, although traditionally recognized for its neurotoxic effects, demonstrates potent antimicrobial properties in our research when genetically expressed in Drosophila. This antimicrobial efficacy is independent of its disulfide bonds and is enhanced when the peptide is membrane-tethered. Apamin selectively inhibits pathogenic bacteria, such as Pseudomonas aeruginosa, Enterococcus faecalis, and Escherichia coli, while promoting beneficial bacteria like Lactobacillus plantarum, thereby improving the gut microbiome. This gut-localized antimicrobial activity is associated with increased intestinal stem cell proliferation, midgut acidification, and enteroendocrine cell calcium signaling. Furthermore, apamin's antimicrobial function relies on specific peptidoglycan recognition proteins, particularly PGRP-LA and PGRP-SCs. Apamin expression alone is sufficient to restore the integrity of the gut barrier compromised by stressful conditions. Ultimately, apamin supplementation enhances honeybee gut health 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 honeybee venom peptides and antimicrobial peptides functions, utilizing the Drosophila model system to unravel their mechanisms of action and therapeutic potential.