Emerging insights into the type I secretion system: a key player in Salmonella virulence and host-pathogen interactions.

Salmonella spp. are major zoonotic bacterial pathogens that can cause a range of diseases in both humans and animals, including gastroenteritis, septicemia, and typhoid fever. During intestinal colonization, Salmonella relies on the coordinated action of the SPI-4 encoded type I secretion system (T1SS) and SPI-1 encoded type III secretion system (T3SS-1) to breach epithelial barriers. Although the T3SS-1 and its effectors have been widely studied, the T1SS and its associated effectors remain poorly characterized. The T1SS-secreted substrate SiiE binds to host cell surface mucins via its bacterial Ig-like (BIg) domain, facilitating the proper positioning of the T3SS-1 and subsequently triggering bacterial internalization. Given the critical role of the T1SS and SiiE in Salmonella virulence, they may serve as promising targets for anti-virulence drug development. In this review, we provide an overview of the current knowledge on the T1SS, including its regulatory mechanisms, channel formation, and the functional properties of SiiE.