A natural compound hyperoside targets Salmonella Typhimurium T3SS needle protein InvG

The antimicrobial actions of natural compounds derived from medicinal plants have been well documented. However, their detailed mechanisms underlying the action against microorganisms remain largely unexplored. Salmonella enterica is a common pathogen causing both gastrointestinal and systemic diseases. In Salmonella enterica, the type III secretion system (T3SS) is employed to export secreted effectors directly to the cytoplasm of host cells. Using a SipA-beta-lactamase reporter, we found that hyperoside (HYP) inhibited the activity of Salmonella T3SS needle protein InvG, prevented damage to host cells and protected mice against Salmonella enterica serovar Typhimurium. It was also observed that HYP binds to InvG directly through hydrogen-bridged cations and hydrophobic interactions. The unique mechanism of antibacterial action of HYP suggested that it could be used as a potentially effective candidate for future antimicrobial regimens.