Based on the in-depth study of type III secretion systems (T3SS) in pathogenic bacteria, approaches targeting T3SS have become new alternative strategies to combat drug-resistant bacterial infections. As an important food-borne pathogen, Salmonella enterica serovar Typhimurium (S. Typhimurium) injects effector proteins into host cells through the T3SS to disrupt cell signaling and host responses. In this study, myricetin was screened for its ability to block the translocation function of effector proteins (SipA/SipB) using cell biology and molecular biology methods. It exerted strong effects on inhibiting the expression of Salmonella pathogenicity island 1 (SPI-1)-associated effector proteins without affecting S. Typhimurium growth and thus prevented S. Typhimurium from invading HeLa cells and ultimately inhibited S. Typhimurium-mediated cell damage. In an animal experiment, myricetin comprehensively protected mice from death and pathological damage. A further analysis of the mechanism of action showed that myricetin interfered with the regulatory network of SPI-1-related genes, resulting in a significant decrease in the levels of key effector proteins, and thus inhibited T3SS-mediated virulence. In summary, this study provides a solution for clinical resistance to S. Typhimurium infection and potential candidate compounds. Myricetin, a potential T3SS inhibitor, possesses effective biological activity and exerts protective effects in vitro and in vivo. Myricetin will likely be developed as a novel type of antibiotic targeting S. Typhimurium infections in the future.

基于对致病细菌中III型分泌系统（T3SS）的深入研究，针对T3SS的方法已成为对抗耐药细菌感染的新替代策略。作为一种重要的食物传播病原体，肠沙门氏菌鼠伤寒沙门氏菌（小号。鼠伤寒沙门氏菌）喷射效应蛋白进入宿主细胞通过T3SS破坏细胞信号传导和宿主反应。在这项研究中，使用细胞生物学和分子生物学方法筛选了杨梅素阻断效应蛋白（SipA / SipB）转运功能的能力。它在抑制沙门氏菌致病岛1（SPI-1）相关效应蛋白的表达方面发挥了强大作用，而不会影响S。鼠伤寒沙门氏菌的生长和因而防止小号。鼠伤寒沙门氏菌侵入HeLa细胞，并最终抑制小号。鼠伤寒介导的细胞损伤。在动物实验中，杨梅素全面保护小鼠免受死亡和病理损害。对作用机理的进一步分析表明，杨梅素干扰了SPI-1相关基因的调控网络，导致关键效应蛋白水平显着下降，从而抑制了T3SS介导的毒力。总而言之，这项研究为临床对S的耐药性提供了解决方案。鼠伤寒感染和潜在的候选化合物。杨梅素是潜在的T3SS抑制剂，具有有效的生物学活性并在体外发挥保护作用和体内。杨梅素将可能被开发为靶向S的新型抗生素。将来发生鼠伤寒感染。