Screening of Potential Drug Targets Based on the Genome-Scale Metabolic Network Model of Vibrio parahaemolyticus

TL;DR

This study uses a genome-scale model to identify essential metabolites in Vibrio parahaemolyticus as potential targets for new antibiotics.

Contribution

A new genome-scale metabolic network model of V. parahaemolyticus is reconstructed and used to screen essential drug targets.

Findings

10 essential metabolites critical for V. parahaemolyticus survival were identified.

39 structural analogs of the essential metabolites were found for drug design.

Molecular docking analysis confirmed the potential of these metabolites for antimicrobial development.

Abstract

Vibrio parahaemolyticus is a pathogenic bacterium widely distributed in marine environments, posing significant threats to aquatic organisms and human health. The overuse and misuse of antibiotics has led to the development of multidrug- and pan-resistant V. parahaemolyticus strains. There is an urgent need for novel antibacterial therapies with innovative mechanisms of action. In this work, a genome-scale metabolic network model (GMSN) of V. parahaemolyticus, named VPA2061, was reconstructed to predict the metabolites that can be explored as potential drug targets for eliminating V. parahaemolyticus infections. The model comprises 2061 reactions and 1812 metabolites. Through essential metabolite analysis and pathogen–host association screening with VPA2061, 10 essential metabolites critical for the survival of V. parahaemolyticus were identified, which may serve as key candidates for developing new antimicrobial strategies. Additionally, 39 structural analogs were found for these essential metabolites. The molecular docking analysis of the essential metabolites and structural analogs further investigated the potential value of these metabolites for drug design. The GSMN reconstructed in this work provides a new tool for understanding the pathogenic mechanisms of V. parahaemolyticus. Furthermore, the analysis results regarding the essential metabolites hold profound implications for the development of novel antibacterial therapies for V. parahaemolyticus-related disease.

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