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International journal of molecular sciences
Dec 17, 2020;21 (24):

Dual Antibacterial Activities and Biofilm Eradication of a Marine Peptide-N6NH and Its Analogs against Multidrug-Resistant .

Ting Li, Zhenlong Wang, Huihui Han, Da Teng, Ruoyu Mao, Ya Hao, Na Yang, Xiumin Wang, Jianhua Wang
Author Information
  1. Ting Li: Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
  2. Zhenlong Wang: Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
  3. Huihui Han: Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
  4. Da Teng: Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
  5. Ruoyu Mao: Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
  6. Ya Hao: Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
  7. Na Yang: Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
  8. Xiumin Wang: Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
  9. Jianhua Wang: Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China. ORCID
PMID: 33348848 DOI: 10.3390/ijms21249637

Abstract

is one of the main pathogens causing various diseases in humans and animals. It is currently difficult to eradicate drug-resistant due to the biofilm formation by conventional antibiotic treatments. In this study, a marine peptide-N6NH and its analogs were generated by introducing Orn or replacing with D-amino acids, Val and Pro; their enzymic stability and antibacterial/antibiofilm ability against multi-drug resistant (MDR) ACCC61732 were detected in vitro and in vivo, respectively. The results showed that DN6NH more rapidly killed ACCC61732 and had higher stability in trypsin, simulated gastric/intestinal fluid, proteinase K, and mouse serum than the parent peptide-N6NH. DN6NH and other analogs significantly improved the ability of N6NH to penetrate the outer membrane of ACCC61732. DN6NH, N6PNH and V112N6NH protected mice from catheter-associated biofilm infection with MDR ACCC61732, superior to N6NH and CIP. DN6NH had more potent efficacy at a dose of 5 μmol/kg (100% survival) in a mouse peritonitis model than other analogs (50-66.67%) and CIP (83.33%), and it inhibited the bacterial translocation, downregulated pro-inflammatory cytokines, upregulated the anti-inflammatory cytokine, and ameliorated multiple-organ injuries (including the liver, spleen, lung, and kidney). These data suggest that the analogs of N6NH may be a candidate for novel antimicrobial and antibiofilm agents against MDR infections.

Keywords

Aeromonas veronii antimicrobial activity biofilm marine peptide-N6NH2 non-coded amino acid

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Grants

  1. 31772640/National Natural Science Foundation of China
  2. 31572444/National Natural Science Foundation of China
  3. 31572445/National Natural Science Foundation of China
  4. CAAS-ZDXT2018008/Key Project of Alternatives to Antibiotic for Feed Usages from Chinese Academy of Agricultural Sciences

MeSH Term

Aeromonas veronii
Animals
Anti-Bacterial Agents
Biofilms
Drug Resistance, Multiple
Female
Gram-Negative Bacterial Infections
Mice
Mice, Inbred ICR
Microbial Sensitivity Tests
Multiple Organ Failure
Skin Ulcer

Chemicals

Anti-Bacterial Agents
Journal Article

Word Cloud

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