Myricetin inhibits the type III secretion system of Salmonella enterica serovar typhimurium by downregulating the Salmonella pathogenic island I gene regulatory pathway

• Published in: Microbial pathogenesis 2021-01, Vol.150, p.104695-104695, Article 104695
• Main Authors: Lv, Qianghua, Lv, Yuanzhi, Dou, Xinyi, Wassy, Soromou Lanan, Jia, Guobin, Wei, Lijuan, Yu, Qinlei, Deng, Xuming, Zhang, Chuanjin, Wang, Jianfeng
• Format: Article
• Language: English
• Subjects: Inhibitor; Myricetin; S. Typhimurium; SPI-1; T3SS
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2020.104695

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. •Myricetin inhibited the translocation of the effector proteins and affected the T3SS functions.•Myricetin reduced the Salmonella-mediated cell damage, and provided a comprehensive protective effect on infected mice.•Myricetin inhibited SPI-1 effector proteins expression through the hilD-hilC-rstA-hilA regulatory pathway.