Molecular strategies of Salmonella Typhimurium: from host cell invasion and metabolic hijacking to immune evasion.

Salmonella enterica serovar Typhimurium (S. Typhimurium), a prevalent zoonotic pathogenic bacterium, has its pathogenicity and intracellular parasitic mechanisms intricately linked to a range of virulence factors. S. Typhimurium infects the host mainly through the type III secretion system (T3SS), with SPI-1-encoded T3SS mediating bacterial internalization and host cytoskeletal remodeling, while SPI-2-encoded T3SS maintains the stability of bacterial-containing vesicles (SCVs) by inhibiting lysosomal fusion. Moreover, the type VI secretion system (T6SS) aids S. Typhimurium in competing with other microorganisms and facilitates its ability to traverse the mucus layer for host colonization, with flagella also contributing significantly to this process. Various effector proteins, secreted by S. Typhimurium, help preserve membrane stability for intracellular survival. To sustain intracellular viability, S. Typhimurium stabilizes its membranes by releasing multiple effector proteins. It sustains the homeostasis of its intracellular living environment by hijacking the host's glycolytic metabolism and suppressing immune responses. At the same time, S. Typhimurium also uses the bidirectional regulation of the autophagy pathway and the co-regulation of apoptosis and pyroptosis programs to construct complex immune escape routes. Our primary objective is to integrate cutting-edge research on S. Typhimurium's parasitism within host cells and the bidirectional mechanisms governing its coexistence with the host. Our focus lies on secretion systems, metabolic reprogramming, and immune evasion, which could provide new perspectives for developing approaches to combat and manage S. Typhimurium.