Potent dual-function of marine peptide N6NH2 and its D-enantiomer to combat MDR A. veronii infection in tilapia (GIFT, Oreochromis niloticus).

Tilapia (GIFT, Oreochromis niloticus) has been an economically important freshwater species in China because of its high-quality meat, high yield and high fertility, etc. At present, the high-density breeding industry has suffered great damage from Aeromonas veronii (A. veronii) infections, and the extensive use of antibiotics in aquaculture has resulted in the prevalence of antibiotic-resistant bacteria, resulting in huge economic losses. In this study, we investigated the antibacterial effect of a marine peptide-N6NH2 and its D-enantiomer (DN6NH2) on acute A. veronii infections of O. niloticus models, with traditional veterinary antibiotics as controls and found that the DN6NH2 had stronger antibacterial activity in vivo than the parent peptide N6NH2 and florfenicol. The mortality results showed that DN6NH2 had more potent efficacy at a dose of 10 mg/kg (81.82 % survival) in O. niloticus peritoneal infection model than 10 mg/kg N6NH2 (51.52 %) and 10 mg/kg florfenicol (30.30 %). Histopathologic changes observed by HE staining showed significant alleviation in the DN6NH2 group, inflammation, bleeding and necrosis of the liver, intestine, spleen and gills have been reduced. In addition, in the spleen and head kidney, DN6NH2 was effective in alleviating the strong immune response to A. veronii infection in O. niloticus by real-time quantitative RT-PCR. In addition, DN6NH2 significantly reduced nuclear factor-kappaB p65 (NF-κB p65) levels in the spleen after A. veronii infection, indicating its good immunomodulatory capacity. These results suggest the protective action of DN6NH2 against A. veronii and the potential of this peptide as a promising candidate for aquaculture applications.