Aspartate metabolic flux promotes nitric oxide to eliminate both antibiotic-sensitive and -resistantin zebrafish.

Abstract

INTRODUCTION: 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. METHODS: The reprogramming metabolome approach was adopted to characterize the metabolic state of zebrafish infected with tetracycline-sensitive and -resistantand to identify overlapping depressed metabolite in dying zebrafish as a reprogramming metabolite. RESULTS: 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. 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 -resistantis 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. DISCUSSION: These findings support the conclusion that aspartate plays an important protective role through NO against both types of. Importantly, we found that tetracycline-sensitive and -resistantare sensitive to NO. Therefore, aspartate is an effective reprogramming metabolite that allows implementation of an antibiotic-free approach against bacterial pathogens.