Salmonella Typhimurium Lacking YjeK as a Candidate Live Attenuated Vaccine Against Invasive Salmonella Infection

초록

Non-typhoidalSalmonella(NTS) causes gastrointestinal infection, which is commonly self-limiting in healthy humans but may lead to invasive infection at extraintestinal sites, leading to bacteremia and focal systemic infections in the immunocompromised. However, a prophylactic vaccine against invasive NTS has not yet been developed. In this work, we explored the potential of a Delta yjeKmutant strain as a live attenuated vaccine against invasive NTS infection. YjeK in combination with YjeA is required for the post-translational modification of elongation factor P (EF-P), which is critical for bacterial protein synthesis. Therefore, malfunction of YjeK and YjeA-mediated EF-P activation might extensively influence protein expression duringSalmonellainfection.Salmonellalacking YjeK showed substantial alterations in bacterial motility, antibiotics resistance, and virulence. Interestingly, deletion of theyjeKgene increased the expression levels ofSalmonellapathogenicity island (SPI)-1 genes but decreased the transcription levels of SPI-2 genes, thereby influencing bacterial invasion and survival abilities in contact with host cells. In a mouse model, the Delta yjeKmutant strain alleviated the levels of splenomegaly and bacterial burdens in the spleen and liver in comparison with the wild-type strain. However, mice immunized with the Delta yjeKmutant displayed increased Th1- and Th2-mediated immune responses at 28 days post-infection, promoting cytokines and antibodies production. Notably, the Th2-associated antibody response was highly induced by administration of the Delta yjeKmutant strain. Consequently, vaccination with the Delta yjeKmutant strain protected 100% of the mice against challenge with lethal invasiveSalmonellaand significantly relieved bacterial burdens in the organs. Collectively, these results suggest that the Delta yjeKmutant strain can be exploited as a promising live attenuated NTS vaccine.

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