Improved Stability and Activity of a Marine Peptide-N6NH2 against <i>Edwardsiella tarda</i> and Its Preliminary Application in Fish
<i>Edwardsiella tarda</i> 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 wa...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/18/12/650 |
| _version_ | 1797544365384531968 |
|---|---|
| author | Huihui Han Ting Li Zhenlong Wang Da Teng Ruoyu Mao Ya Hao Na Yang Xiumin Wang Jianhua Wang |
| author_facet | Huihui Han Ting Li Zhenlong Wang Da Teng Ruoyu Mao Ya Hao Na Yang Xiumin Wang Jianhua Wang |
| author_sort | Huihui Han |
| collection | DOAJ |
| description | <i>Edwardsiella tarda</i> 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 <i>E. tarda</i> 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 <i>E. tarda</i> were 1.29–3.2 μM. Both N6 and N6NH2 killed bacteria by destroying the cell membrane of <i>E. tarda</i> 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 <i>E. tarda</i>, 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 <i>E. tarda</i> infections. |
| first_indexed | 2024-03-10T13:59:26Z |
| format | Article |
| id | doaj.art-c087f33e5e64452bbcc8bad17f6ed393 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T13:59:26Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-c087f33e5e64452bbcc8bad17f6ed3932023-11-21T01:17:13ZengMDPI AGMarine Drugs1660-33972020-12-01181265010.3390/md18120650Improved Stability and Activity of a Marine Peptide-N6NH2 against <i>Edwardsiella tarda</i> and Its Preliminary Application in FishHuihui Han0Ting Li1Zhenlong Wang2Da Teng3Ruoyu Mao4Ya Hao5Na Yang6Xiumin Wang7Jianhua Wang8Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, 12 Zhongguancun Nandajie St., Haidian District, Beijing 100081, ChinaGene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, 12 Zhongguancun Nandajie St., Haidian District, Beijing 100081, ChinaGene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, 12 Zhongguancun Nandajie St., Haidian District, Beijing 100081, ChinaGene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, 12 Zhongguancun Nandajie St., Haidian District, Beijing 100081, ChinaGene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, 12 Zhongguancun Nandajie St., Haidian District, Beijing 100081, ChinaGene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, 12 Zhongguancun Nandajie St., Haidian District, Beijing 100081, ChinaGene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, 12 Zhongguancun Nandajie St., Haidian District, Beijing 100081, ChinaKey Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, ChinaGene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, 12 Zhongguancun Nandajie St., Haidian District, Beijing 100081, China<i>Edwardsiella tarda</i> 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 <i>E. tarda</i> 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 <i>E. tarda</i> were 1.29–3.2 μM. Both N6 and N6NH2 killed bacteria by destroying the cell membrane of <i>E. tarda</i> 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 <i>E. tarda</i>, 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 <i>E. tarda</i> infections.https://www.mdpi.com/1660-3397/18/12/650marine peptideN6N6NH2antimicrobial activitymechanism<i>Edwardsiella tarda</i> |
| spellingShingle | Huihui Han Ting Li Zhenlong Wang Da Teng Ruoyu Mao Ya Hao Na Yang Xiumin Wang Jianhua Wang Improved Stability and Activity of a Marine Peptide-N6NH2 against <i>Edwardsiella tarda</i> and Its Preliminary Application in Fish Marine Drugs marine peptide N6 N6NH2 antimicrobial activity mechanism <i>Edwardsiella tarda</i> |
| title | Improved Stability and Activity of a Marine Peptide-N6NH2 against <i>Edwardsiella tarda</i> and Its Preliminary Application in Fish |
| title_full | Improved Stability and Activity of a Marine Peptide-N6NH2 against <i>Edwardsiella tarda</i> and Its Preliminary Application in Fish |
| title_fullStr | Improved Stability and Activity of a Marine Peptide-N6NH2 against <i>Edwardsiella tarda</i> and Its Preliminary Application in Fish |
| title_full_unstemmed | Improved Stability and Activity of a Marine Peptide-N6NH2 against <i>Edwardsiella tarda</i> and Its Preliminary Application in Fish |
| title_short | Improved Stability and Activity of a Marine Peptide-N6NH2 against <i>Edwardsiella tarda</i> and Its Preliminary Application in Fish |
| title_sort | improved stability and activity of a marine peptide n6nh2 against i edwardsiella tarda i and its preliminary application in fish |
| topic | marine peptide N6 N6NH2 antimicrobial activity mechanism <i>Edwardsiella tarda</i> |
| url | https://www.mdpi.com/1660-3397/18/12/650 |
| work_keys_str_mv | AT huihuihan improvedstabilityandactivityofamarinepeptiden6nh2againstiedwardsiellatardaianditspreliminaryapplicationinfish AT tingli improvedstabilityandactivityofamarinepeptiden6nh2againstiedwardsiellatardaianditspreliminaryapplicationinfish AT zhenlongwang improvedstabilityandactivityofamarinepeptiden6nh2againstiedwardsiellatardaianditspreliminaryapplicationinfish AT dateng improvedstabilityandactivityofamarinepeptiden6nh2againstiedwardsiellatardaianditspreliminaryapplicationinfish AT ruoyumao improvedstabilityandactivityofamarinepeptiden6nh2againstiedwardsiellatardaianditspreliminaryapplicationinfish AT yahao improvedstabilityandactivityofamarinepeptiden6nh2againstiedwardsiellatardaianditspreliminaryapplicationinfish AT nayang improvedstabilityandactivityofamarinepeptiden6nh2againstiedwardsiellatardaianditspreliminaryapplicationinfish AT xiuminwang improvedstabilityandactivityofamarinepeptiden6nh2againstiedwardsiellatardaianditspreliminaryapplicationinfish AT jianhuawang improvedstabilityandactivityofamarinepeptiden6nh2againstiedwardsiellatardaianditspreliminaryapplicationinfish |