Functional regulation and cross-talk of type III and type VI secretion systems in Salmonella

In Salmonella, the type III and type VI secretion systems (T3SS and T6SS) play critical roles in pathogenicity. The bacterium harbors two distinct T3SSs: T3SS-1, encoded by SPI-1, promotes host cell invasion, whereas T3SS-2 (located within SPI-2) facilitates systemic infection. Both systems translocate effector proteins that disrupt normal host cell functions. Meanwhile, the T6SS enhances competitive fitness in the gut by targeting rival bacteria and supports evasion of the host immune response. Recent evidence indicates that these secretion systems share common regulatory components, including the PhoP-PhoQ and PmrA-PmrB two-component systems, as well as signaling molecules such as cyclic di-GMP (c-di-GMP), allowing coordinated activation and functional adaptation during infection. However, the precise mechanisms governing their crosstalk remain poorly understood. This review summarizes the current knowledge of the composition, function, and regulation of T3SS and T6SS in Salmonella, examines their interplay, and provides perspectives for future research into pathogenesis.