National Key Laboratory of Green Pesticide, Integrative Microbiology Research Centre, Guangdong Province Key Laboratory of Microbial Signals and Disease Control, College of Plant Protection, South China Agricultural University, Guangzhou 510642, China.
College of Materials and Energy, South China Agricultural University, Guangzhou 510642, China.
J Agric Food Chem. 2024 Aug 7;72(31):17210-17218. doi: 10.1021/acs.jafc.4c02277. Epub 2024 Jul 26.
To identify potent inhibitors of the type III secretion system (T3SS) in the foodborne pathogen , we synthesized 35 thiazole-containing aryl amides by merging salicylic acid with various heterocycles through active splicing. Screening for promoter activity led to the discovery of a highly effective T3SS inhibitor from these 35 compounds. Through subsequent experiments, it was confirmed that compound specifically targeted the T3SS of . Additionally, compound inhibited the secretion of the effector protein ExoS by modulating the CyaB-cAMP/Vfr-ExsA and ExsCED-ExsA regulatory pathways. Furthermore, compound suppressed the transcription of genes involved in the needle complex assembly, leading to reduced bacterial virulence. Further validation through inoculation tests using larvae demonstrated the strong in vivo efficacy of compound . The study also revealed that compound enhanced the bactericidal activity of antibiotics, such as CIP (ciprofloxacin) and TOB (tobramycin). These results could help develop novel antimicrobial drugs to reduce bacterial resistance.
为了在食源性病原体中鉴定出有效的 III 型分泌系统 (T3SS) 抑制剂，我们通过活性拼接将水杨酸与各种杂环融合，合成了 35 种含噻唑的芳基酰胺。筛选启动子活性导致从这 35 种化合物中发现了一种高效的 T3SS 抑制剂。通过后续实验，证实化合物 特异性靶向 的 T3SS。此外，化合物 通过调节 CyaB-cAMP/Vfr-ExsA 和 ExsCED-ExsA 调节途径抑制效应蛋白 ExoS 的分泌。此外，化合物 抑制参与针复合物组装的基因的转录，从而降低细菌毒力。使用 幼虫进行接种试验的进一步验证表明化合物 的体内疗效很强。该研究还表明，化合物 增强了抗生素（如 CIP（环丙沙星）和 TOB（妥布霉素））的杀菌活性。这些结果有助于开发新型抗菌药物以减少细菌耐药性。
