1. Metabolic Flux Analysis of Xanthomonas oryzae Treated with Bismerthiazol Revealed Glutathione Oxidoreductase in Glutathione Metabolism Serves as an Effective Target.
- Author
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Yu HL, Liang XL, Ge ZY, Zhang Z, Ruan Y, Tang H, and Zhang QY
- Subjects
- Glutathione Reductase metabolism, Glutathione Reductase genetics, Metabolic Flux Analysis, Plant Diseases microbiology, Thiazoles pharmacology, Thiazoles metabolism, Bacterial Proteins metabolism, Bacterial Proteins genetics, Metabolic Networks and Pathways drug effects, Gene Expression Regulation, Bacterial drug effects, Sulfhydryl Compounds, Thiadiazoles, Xanthomonas drug effects, Glutathione metabolism, Anti-Bacterial Agents pharmacology, Oryza microbiology, Oryza metabolism
- Abstract
Bacterial blight (BB) of rice caused by Xanthomonas oryzae pathovar oryzae ( Xoo ) is a serious global rice disease. Due to increasing bactericide resistance, developing new inhibitors is urgent. Drug repositioning offers a potential strategy to address this issue. In this study, we integrated transcriptional data into a genome-scale metabolic model (GSMM) to screen novel anti- Xoo targets. Two RNA-seq datasets (before and after bismerthiazol treatment) were used to constrain the GSMM and simulate metabolic processes. Metabolic fluxes were calculated using parsimonious flux balance analysis (pFBA) identifying reactions with significant changes for target screening. Glutathione oxidoreductase (GSR) was selected as a potential anti- Xoo target and validated through antibacterial experiments. Virtual screening based on the target identified DB12411 as a lead compound with the potential for new antibacterial agents. This approach demonstrates that integrating metabolic networks and transcriptional data can aid in both understanding antibacterial mechanisms and discovering novel drug targets.
- Published
- 2024
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