Angelicin Suppresses Salmonella Virulence Through SirA-Mediated Inhibition of Type I and Type III secretion systems

Salmonella is a leading cause of foodborne illnesses. The overuse of antibiotics has led to the widespread emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, posing a significant threat to public health security. Overcoming this healthcare crisis requires new approaches in antibiotic discovery and the identification of unique bacterial targets. In this study, we identified Angelicin (AL), a natural compound, as a non-antibacterial inhibitor targeting both Salmonella T1SS and T3SS-1. AL inhibits the transcription of sirA, thereby suppressing hilD transcription, and further disrupts T1SS and T3SS-1 dependent invasion of Salmonella by down-regulating HilA expression. Cell-based experiments and mouse models of infection demonstrate that AL attenuates Salmonella virulence in vitro and in vivo. Our findings suggest that AL might be served as a promising lead compound for the development of anti-virulence agents against Salmonella infection by targeting both T1SS and T3SS-1.