Structural Analysis of Salmonella Type III Secretion System and Research Progress on Its Inhibitors

Abstract

Background: Salmonella is the second most prevalent foodborne pathogen globally, with multidrug resistance increasing by 1.84%-2.69% annually in China, necessitating non-antibiotic therapies. This review aims to analyze the structure and regulatory mechanisms of “Salmonella” Type III Secretion System (T3SS) and advance inhibitor development. We summarize structural insights into T3SS components (basal body, needle complex, transmembrane pore) encoded by SPI-1/SPI-2 pathogenicity islands, and the HilC-RtsA-HilD regulatory network controlling invasion. Key inhibitors demonstrate multi-mechanistic efficacy: salicylidene hydrazides (e.g., INP0007) block effector translocation; Camino side A specifically inhibits T3SS secretion (IC₅₀=20 μM); flavonoids (quercetin/fisetin) suppress SPI-1 genes (hilA, sopA) and disrupt HilD regulator activity, reducing bacterial colonization in vivo by >50%. ATPase SctN/InvC is identified as a novel target. Conclusion: T3SS inhibitors exhibit potent anti-virulence effects with low resistance development, providing promising alternatives to conventional antibiotics.