PUBLICATION

Phenylalanine enhances innate immune response to clear ceftazidime-resistant Vibrio alginolyticus in Danio rerio

Authors
Jiang, M., Gong, Q.Y., Lai, S.S., Cheng, Z.X., Chen, Z.G., Zheng, J., Peng, B.
ID
ZDB-PUB-181106-5
Date
2018
Source
Fish & shellfish immunology   84: 912-919 (Journal)
Registered Authors
Keywords
Ceftazidime resistance, Innate immune response, Metabolomics, Phenylalanine, Vibrio alginolyticus
MeSH Terms
  • Animals
  • Anti-Bacterial Agents/pharmacology*
  • Ceftazidime/pharmacology*
  • Drug Resistance, Bacterial/immunology*
  • Fish Diseases/immunology
  • Immunity, Innate/genetics
  • Microbial Sensitivity Tests
  • Phenylalanine/metabolism*
  • Vibrio Infections/immunology
  • Vibrio alginolyticus/drug effects*
  • Vibrio alginolyticus/physiology
  • Zebrafish/genetics*
  • Zebrafish/immunology*
PubMed
30389644 Full text @ Fish Shellfish Immunol.
Abstract
Antibiotic-resistant bacteria becomes a major threat to the economy and food safety in aquaculture. Although the antibiotic-dependent strategy is still the mostly adopted option, the development of antibiotic-free approach is urgently needed to ameliorate the severe situation of the global antibiotic resistance. In the present study, we showed that modulating the metabolism of zebrafish, Danio reiro, would enhance D. rerio to clear ceftazidime-resistant Vibrio alginoyticus (Caz-R) in vivo. By generating Caz-R in vitro, we found Caz-R stays longer than ceftazidime-sensitive V. alginoyticus (Caz-S) in D. rerio, where Caz-R induced less potent immune response than that of Caz-S. The differential immune response was associated with different metabolism of the host. Through functional metabolomics, we identified a crucial biomarker, phenylalanine. The abundance of phenylalanine was increased in both of Caz-S and Caz-R infected hosts but the abundance was higher in Caz-S infected group. This specific difference indicated phenylalanine could be a metabolite required to clear Caz-R by the host. Exogenous phenylalanine would enhance the host's ability to remove Caz-R, which was through upregulated production of lysozyme and C3b. Thus, our study demonstrates a novel strategy to boost host's immune response to combat against antibiotic-resistant bacteria.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping