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.