Abstract
Salmonella Typhimurium is an invasive intracellular pathogen that employs various factors for its survival within host cells. To mitigate S. Typhimurium survival, it is crucial to identify factors that influence bacterial survival and to develop drugs that inhibit these factors. In this study, we investigated the effects of nafcillin and diosmin, both of which have been identified as inhibitors of Lon protease, on the intracellular survival of S. Typhimurium and its survival under various stress conditions. Additionally, we examined the expression of genes associated with the type II toxin-antitoxin system to enhance our understanding of the impact of these systems on the bacterium's survival. Our findings indicate that while nafcillin and diosmin did not affect S. Typhimurium attachment, they significantly reduced bacterial intracellular survival, particularly in Hep2 cells after 16 h. These inhibitors were also effective in decreasing bacterial survival under oxidative and acidic stress conditions. Furthermore, gene expression analysis revealed that although there were variations in the expression of TA system genes in S. Typhimurium across different cell lines, the relEB system emerged as the most effective among those studied, exhibiting the highest increase in expression. This study highlights the efficacy of nafcillin and diosmin in reducing the intracellular survival of S. Typhimurium as well as its survival under stress conditions. These findings suggest potential new strategies for developing therapies aimed at preventing S. Typhimurium infections.