Design and Synthesis of Aryl Amide Derivatives Containing Thiazole as Type III Secretion System Inhibitors against .

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.