PUBLICATION

Aspartate metabolic flux promotes nitric oxide to eliminate both antibiotic-sensitive and -resistant Edwardsiella tarda in zebrafish

Authors
Xiang, J., Li, M.Y., Li, H.
ID
ZDB-PUB-231027-64
Date
2023
Source
Frontiers in immunology   14: 12772811277281 (Journal)
Registered Authors
Keywords
Edwardsiella tarda, antibiotic-free approach, aspartate, nitric oxide, reprogramming metabolome, sodium nitroprusside, zebrafish
MeSH Terms
  • Animals
  • Anti-Bacterial Agents/pharmacology
  • Aspartic Acid/pharmacology
  • Bacteria
  • Edwardsiella tarda
  • Enterobacteriaceae Infections*
  • Fish Diseases*
  • Nitric Oxide
  • Tetracyclines
  • Zebrafish
PubMed
37885884 Full text @ Front Immunol
Abstract
Metabolic reprogramming potentiates host protection against antibiotic-sensitive or -resistant bacteria. However, it remains unclear whether a single reprogramming metabolite is effective enough to combat both antibiotic-sensitive and -resistant bacteria. This knowledge is key for implementing an antibiotic-free approach.
The reprogramming metabolome approach was adopted to characterize the metabolic state of zebrafish infected with tetracycline-sensitive and -resistant Edwardsiella tarda and to identify overlapping depressed metabolite in dying zebrafish as a reprogramming metabolite.
Aspartate was identify overlapping depressed metabolite in dying zebrafish as a reprogramming metabolite. Exogenous aspartate protects zebrafish against infection caused by tetracycline-sensitive and -resistant E. tarda. Mechanistically, exogenous aspartate promotes nitric oxide (NO) biosynthesis. NO is a well-documented factor of promoting innate immunity against bacteria, but whether it can play a role in eliminating both tetracycline-sensitive and -resistant E. tarda is unknown. Thus, in this study, aspartate was replaced with sodium nitroprusside to provide NO, which led to similar aspartate-induced protection against tetracycline-sensitive and -resistant E. tarda.
These findings support the conclusion that aspartate plays an important protective role through NO against both types of E. tarda. Importantly, we found that tetracycline-sensitive and -resistant E. tarda are sensitive to NO. Therefore, aspartate is an effective reprogramming metabolite that allows implementation of an antibiotic-free approach against bacterial pathogens.
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