Natural compound sanguinarine chloride targets the type III secretion system of Salmonella enterica Serovar Typhimurium

The type III secretion system (T3SS) is a key virulence mechanism of many Gram-negative bacterial pathogens. Upon contact between bacteria and host cells, T3SS transfers a series of effectors from the bacterial cytosol to host cells. It is widely known that a mutation in T3SS does not impair bacterial growth, thereby avoiding any subsequent development of resistance. Thus, T3SS is expected to be a candidate therapeutic target. While developing the T3SS screening method, we discovered that sanguinarine chloride, a natural compound, could decrease the production of the SPI-1 type III secretion system main virulence proteins SipA and SipB and prevent the invasion of HeLa cells by Salmonella enterica serovar Typhimurium without affecting the growth of Salmonella. Furthermore, sanguinarine chloride downregulated the transcription of HilA and consequently regulated the expression of the SPI-1 apparatus and effector genes. In summary, our study directly demonstrated that this putative SPI-1 inhibitor belongs to a novel class of anti-Salmonella compounds.