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

Fire blight, caused by <i>Erwinia amylovora</i>, 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 <i>E. amylovora</i>. 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 <i>lux</i> reporter gene. Compound <b>5c</b> was identified as the most effective inhibitor, significantly suppressing the promoter expression of T3SS-related genes, such as <i>hrpA</i> and <i>hrpL</i>, in <i>E. amylovora</i> CFBP1430. Furthermore, compound <b>5c</b> inhibited the hypersensitive response (HR) triggered by <i>E. amylovora</i> CFBP1430 in tobacco without affecting bacterial growth. Compound <b>5c</b> also reduced the level of secretion of the pathogenic protein HrpN and diminished the pathogenicity of <i>E. amylovora</i> 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.