AUTHOR=Xiang Jiao , Li Min-yi , Li Hui 

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1277281

DOI=10.3389/fimmu.2023.1277281

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>The reprogramming metabolome approach was adopted to characterize the metabolic state of zebrafish infected with tetracycline-sensitive and -resistant <italic>Edwardsiella tarda</italic> and to identify overlapping depressed metabolite in dying zebrafish as a reprogramming metabolite.</p></sec><sec><title>Results</title><p>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 <italic>E. tarda</italic>. 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 <italic>E. tarda</italic> 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 <italic>E. tarda</italic>.</p></sec><sec><title>Discussion</title><p>These findings support the conclusion that aspartate plays an important protective role through NO against both types of <italic>E. tarda</italic>. Importantly, we found that tetracycline-sensitive and -resistant <italic>E. tarda</italic> are sensitive to NO. Therefore, aspartate is an effective reprogramming metabolite that allows implementation of an antibiotic-free approach against bacterial pathogens.</p></sec>