Quercitrin Is a Novel Inhibitor of Serovar Typhimurium Type III Secretion System.

The purpose was to screen type III secretory system (T3SS) inhibitors of serovar Typhimurium () from natural compounds. The pharmacological activities and action mechanisms of candidate compounds in vivo and in vitro were systematically studied and analyzed. Using a SipA-β-lactamase fusion reporting system, we found that quercitrin significantly blocked the translocation of SipA into eukaryotic host cells without affecting the growth of bacteria. Adhesion and invasion assay showed that quercitrin inhibited invasion into host cells and reduced mediated host cell damage. β-galactosidase activity detection and Western blot analysis showed that quercitrin significantly inhibited the expression of SPI-1 genes ( and ) and effectors (SipA and SipC). The results of animal experiments showed that quercitrin significantly reduced colony colonization and alleviated the cecum pathological injury of the infected mice. Small molecule inhibitor quercitrin directly inhibited the function of T3SS and provided a potential antibiotic alternative against infection. Importance: T3SS plays a crucial role in the bacterial invasion and pathogenesis of . Compared with conventional antibiotics, small molecules could inhibit the virulence factors represented by T3SS. They have less pressure on bacterial vitality and a lower probability of producing drug resistance. Our results provide strong evidence for the development of novel inhibitors against infection.