Amidated pleurocidin peptide encapsulated in biodegradable poly(lactide-co-glycolide) microparticles sustains its antibacterial activity against Photobacterium damselae subsp. piscicida in cobia

Photobacterium damselae subsp. piscicida (PDP), the causative agent of fish pasteurellosis, has become a serious threat leading to high mortalities in cage-cultured juveniles of cobia (Rachycentron canadum). However, overuse of conventional antibiotics to control the infection raises the emergence of resistant bacteria as well as the presence of residual drugs in animals and the environment. Further efforts are therefore needed to look for new and effective antibacterial agents, such as antimicrobial peptides (AMPs), for use on the fish farm to replace conventional antibiotics before commercial vaccines against PDP are available. In the present study, the fish-derived AMP, pleurocidin (PLE), was used as an anti-PDP agent. After C-terminal amidation, the resulting amidated PLE peptide, PLE(am), was further encapsulated with the poly (lactide-co-glycolide) (PLG) polymer to generate PLG-PLE(am) microparticles that would sustain release of antibacterial PLE(am) and elicit effective protection against PDP in cobia. PLG-PLE(am) microparticles, 4.25–5.39 μm in diameter, contained 14.69–18.47 μg of entrapped PLE(am) per milligram of dry weight of microparticles and showed 81%~84% entrapment efficiency. The amount of released PLE(am) from PLG microparticles gradually increased over a 28-day triphasic controlled-release period and the released PLE(am) still retained its antibacterial activity. Peritoneal injection with PLG-PLE(am) microparticles further protected all cobia from a lethal peritoneal infection of 2 × 10³ CFU PDP (MML-3) and allowed cobia to survive relatively longer (14 days post infection). In conclusion, the sustained release of antibacterial PLE(am) peptide from PLG-PLE(am) microparticles can preserve the antibacterial activity to result in effective protection in cobia. Our study provides notable evidence to indicate the feasibility of using PLG-PLE(am) microparticles as an antibacterial agent against PDP in cobia.