Improved antibacterial activity of fluorinated tjipanazole D derivative on Xanthomonas oryzae pv. oryzae via synergistic multi-mechanism action.

Abstract

Background: Bacterial leaf blight caused by Xanthomonas oryzae pv. oryzae (Xoo) severely threatens global rice yields. With increasing resistance to conventional antibacterial agents, new antibacterial agents are urgently needed. This study aimed to optimize the cyanobacterial metabolite tjipanazole D to develop a derivative with enhanced antibacterial activity against Xoo and evaluate its mechanism of action.

Results: Derivative Y-4-1 was successfully synthesized using a fluorination substitution strategy. This derivative Y-4-1 exhibited significantly enhanced antibacterial efficacy against Xoo (minimum inhibitory concentration = 6.25 μg/mL, compared with 100 μg/mL for tjipanazole D). Mechanistic studies revealed that Y-4-1 exerted its antibacterial effects by disrupting the cell membrane of Xoo, inhibiting xanthomonadin biosynthesis, and aggravating oxidative damage. Furthermore, biofilm formation was inhibited in a dose-dependent way by reducing the production of Xoo extracellular polymers such as exopolysaccharides and extracellular enzymes and inhibiting Xoo motility, and ultimately resulting in bacterial death. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that differentially expressed genes were significantly enriched in key pathways such as plant-pathogen interactions and ribosome biogenesis. Notably, the mechanisms regulating biofilm formation play a crucial role in mediating plant-pathogen interactions.

Conclusion: These findings highlight the potential of Y-4-1 as an antibacterial agent against Xoo and provide new design ideas for the development of next-generation antibacterial agents in sustainable agriculture. However, its field control efficacy and environmental behavior still need further evaluation. © 2026 Society of Chemical Industry.