Tldi1 deficiency mediates Tlde1 self-toxic effect to regulate the adaptability of Salmonella Typhimurium infection and host immune response in mice.

INTRODUCTION: Type VI secretion system (T6SS) is a key bacterial secretion device in Salmonella enterica serovar Typhimurium (S. Typhimurium), responsible for translocating effectors to mediate bacterial-host interaction. Tldi1, a well-characterized immunity protein encoded in the T6SS gene cluster, specifically neutralizes the cognate toxin Tlde1 to prevent bacterial "friendly fire". However, there is still a lack of systematic and in-depth research on the functions of Tldi1 at present. In order to elucidate the phenotype and toxicity effects of Tldi1 deficiency on S. Typhimurium, this study used S. Typhimurium SL1344 as a model strain and explored the role of Tldi1 toxicity on bacterial ecological adaptability and infection process through multi-level experiments.

METHODS: Firstly, molecular bioinformatics approaches were employed to analyze the physicochemical properties, hydrophilicity, hydrophobicity, transmembrane regions, subcellular localization, as well as secondary and tertiary structures of the Tldi1 protein. Secondly, a tldi1-deficient mutant of S. Typhimurium was constructed via homologous double crossover recombination, and alterations in its biological characteristics were analyzed. Finally, a mouse infection model was used to investigate the effect of tldi1 deletion on the infection progression of S. Typhimurium.

RESULTS: The results showed that compared with the wild-type (WT) strain, the Δtldi1 strain exhibited reduced splenic colonization, and regulated host inflammation, while these phenotypes were reversed in the Δtldi1/pΔtldi1 strain.

DISCUSSION: Tldi1, as a key immunity protein for Tlde1 neutralization, indirectly regulates the environmental adaptability and host immune homeostasis of S. Typhimurium, providing new insights into the function of T6SS immunity proteins.