Antibacterial activity and mechanism of novel berberine derivative HBBR‐F4 against Xanthomonas oryzae pv. Oryzae

BACKGROUND: Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of rice bacterial blight, poses a significant threat to global crop security by means of systemic vascular colonization. In order to address emerging resistance challenges, a rational drug design strategy was employed, which involved structurally optimizing the natural alkaloid berberine (BBR). Through a C-9/C-13 dual-site modification approach, we developed a novel berberine derivative, 9-benzoyloxy-13-(4-(tert-butyl)benzyl)-berberine bromide (HBBR-F4). This compound demonstrated exceptional anti-Xoo efficacy, achieving protective and curative effects of 62.57 and 65.23%, respectively, in vivo, outperforming the commercial bactericide thiodiazole copper. RESULTS: HBBR-F4 showed strong antibacterial activity against Xoo with the minimum inhibitory concentration and minimum bactericidal concentration values of 3.12 and 6.25 μg/mL, while showing negligible phytotoxicity. The results of transcriptomics showed that HBBR-F4 could inhibit the amination of cell membrane phospholipids, change the biosynthesis of membrane phospholipids, destroy the lipid balance of bacterial cell membrane, lead to cell membrane damage, intracellular nucleic acid leakage, SOS reaction and other bacterial dysfunction, thus inhibiting bacterial growth. This was confirmed by qRT-PCR and related experiments. Observation of bacterial morphology showed that, following treatment with HBBR-F4, Xoo cells exhibited irregular shapes, dissolved cytoplasms, broken cell membranes and vacuolated cytoplasms. CONCLUSION: HBBR-F4 alters the biosynthetic pathway of membrane phospholipids, disrupting the balance of bacterial cell membranes and causing functional damage to Xoo, making it a sustainable solution for the prevention and control of bacterial blight of rice. © 2025 Society of Chemical Industry.