Avian [beta]-defensins as antimicrobial and immunomodulatory agents

Abstract

The increasing prevalence of antibiotic-resistance and lack of effective antibiotics pose a serious threat to animal health and public health. Host antimicrobial peptides (AMPs) show broad-spectrum antimicrobial activity against various microbes with low potential for resistance development, compared to conventional antibiotics, indicating great potentials as therapeutic agents. Despite such promise, several limitations hinder the application of AMPs in the clinic, including high manufacturing cost, cytotoxicity, and stability in physiological conditions. New strategies are needed to solve those problems for their application. Avian beta-defensins (AvBD) are small, cationic, antimicrobial peptides. The potential application of AvBDs as antibiotic alternatives against antibiotic-resistant and zoonotic bacterial pathogens has been the subject of interest. In the first study, the biological functions of two AvBDs, AvBD-6 and AvBD-12, were determined under various experimental conditions. The results showed that AvBD-6 (+7) was more potent than AvBD-12 (+1) against E. coli, S. Typhimurium, and S. aureus as well as clinical isolates of extended-spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumoniae. The antibacterial activity of AvBDs was greatly compromised under physiological salt concentrations. Both AvBDs demonstrated mild chemotactic property for chicken macrophages and AvBD-12, at relatively high concentrations, could also induce the migration of murine immature dendritic cells. The chemotactic property required the presence of chemokine receptor 2 (CCR2) on host cells and the conserved disulfide bridges of the peptides. The two AvBDs were nontoxic to CHO-K1, macrophages, or immature dendritic cells.