Journal Article

Improved Stability and Activity of a Marine Peptide-N6NH2 against Edwardsiella tarda and Its Preliminary Application in Fish

Yang, Na, Wang, Jianhua, Hao, Ya, Teng, Da, Mao, Ruoyu, Wang, Xiumin, Li, Ting, Wang, Zhenlong, Han, Huihui

2020

Overview

Edwardsiella tarda can cause fatal gastro-/extraintestinal diseases in fish and humans. Overuse of antibiotics has led to antibiotic resistance and contamination in the environment, which highlights the need to find new antimicrobial agents. In this study, the marine peptide-N6 was amidated at its C-terminus to generate N6NH2. The antibacterial activity of N6 and N6NH2 against E. tarda was evaluated in vitro and in vivo; their stability, toxicity and mode of action were also determined. Minimal inhibitory concentrations (MICs) of N6 and N6NH2 against E. tarda were 1.29–3.2 μM. Both N6 and N6NH2 killed bacteria by destroying the cell membrane of E. tarda and binding to lipopolysaccharide (LPS) and genomic DNA. In contrast with N6, N6NH2 improved the stability toward trypsin, reduced hemolysis (by 0.19% at a concentration of 256 μg/mL) and enhanced the ability to penetrate the bacterial outer and inner membrane. In the model of fish peritonitis caused by E. tarda, superior to norfloxacin, N6NH2 improved the survival rate of fish, reduced the bacterial load on the organs, alleviated the organ injury and regulated the immunity of the liver and kidney. These data suggest that the marine peptide N6NH2 may be a candidate for novel antimicrobial agents against E. tarda infections.

• Publisher: MDPI AG,MDPI
• Subject: Animals / Anti-Bacterial Agents - chemistry / Anti-Bacterial Agents - pharmacology / Antibacterial activity / antibacterial properties / Antibiotic resistance / Antibiotics / antimicrobial activity / Antimicrobial agents / Antimicrobial Cationic Peptides - chemistry / Antimicrobial Cationic Peptides - pharmacology / Bacteria / Biocompatibility / Body organs / C-Terminus / Cell Membrane - drug effects / Cell membranes / Contamination / Cytotoxicity / Deoxyribonucleic acid / Disease resistance / DNA / Drug resistance / Edwardsiella tarda / Edwardsiella tarda - drug effects / Enterobacteriaceae Infections - drug therapy / Enterobacteriaceae Infections - microbiology / Enterobacteriaceae Infections - virology / environment / Fish / Fish diseases / Fish Diseases - drug therapy / Fish Diseases - microbiology / Fish Diseases - pathology / Fish Proteins / Genomics / Gram-negative bacteria / Gram-positive bacteria / Haemolysis / hemolysis / humans / Immunity / In vivo methods and tests / Injury prevention / Kidney - pathology / kidneys / Lipopolysaccharides / liver / Liver - pathology / Load distribution / marine peptide / mechanism / mechanism of action / microbial load / Microbial Sensitivity Tests / minimum inhibitory concentration / Mode of action / N6NH2 / Norfloxacin / Norfloxacin - therapeutic use / Organs / Peptides / Peritonitis / Peritonitis - drug therapy / Peritonitis - etiology / Spectrum analysis / Stability / Stability analysis / Structure-Activity Relationship / Survival / Survival Analysis / survival rate / Toxicity / Trypsin / Wounds