Synthesis and Biological Evaluation of Disulfides Based on Garlic Extract as Type III Secretion System Inhibitors against Erwinia amylovora

Fire blight, caused by Erwinia amylovora, poses a significant threat to rosaceous plants, such as pears, apples, and hawthorns. The type III secretion system (T3SS) is a critical pathogenicity factor in the pathogenesis of E. amylovora. Disulfide compounds, including those derived from garlic extract, exhibit good bioactivity against both bacteria and fungi. In this study, we synthesized 39 disulfide compounds based on garlic extract and developed a high-throughput screening system incorporating the bacterial luciferase lux reporter gene. Compound 5c was identified as the most effective inhibitor, significantly suppressing the promoter expression of T3SS-related genes, such as hrpA and hrpL, in E. amylovora CFBP1430. Furthermore, compound 5c inhibited the hypersensitive response (HR) triggered by E. amylovora CFBP1430 in tobacco without affecting bacterial growth. Compound 5c also reduced the level of secretion of the pathogenic protein HrpN and diminished the pathogenicity of E. amylovora CFBP1430 in pear infection assays. These findings offer a theoretical foundation for the development of novel T3SS inhibitors aimed at the prevention and control of fire blight disease.