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The  speG  gene has been reported to regulate polyamine metabolism in  Escherichia coli  and  Shigella , but its role in  Salmonella  remains unknown. Our preliminary studies have revealed that  speG  widely affects the transcriptomes of infected  in vitro  M and Caco-2 cells and that it is required for the intracellular replication of  Salmonella enterica  serovar Typhimurium ( S . Typhimurium) in HeLa cells. In this study, we demonstrated that  speG  plays a time-dependent and cell type-independent role in the intracellular replication of  S . Typhimurium. Moreover, high-performance liquid chromatography (HPLC) of four major polyamines demonstrated putrescine, spermine, and cadaverine as the leading polyamines in  S . Typhimurium. The deletion of  speG  significantly increased the levels of the three polyamines in intracellular  S . Typhimurium, suggesting the inhibitory effect of  speG  on the biosynthesis of these polyamines. The deletion of  speG  was associated with elevated levels of these polyamines in the attenuated intracellular replication of  S . Typhimurium in host cells. This result was subsequently validated by the dose-dependent suppression of intracellular proliferation after the addition of the polyamines. Furthermore, our RNA transcriptome analysis of  S . Typhimurium SL1344 and its  speG  mutant outside and inside Caco-2 cells revealed that  speG  regulates the genes associated with flagellar biosynthesis, fimbrial expression, and functions of types III and I secretion systems.  speG  also affects the expression of genes that have been rarely reported to correlate with polyamine metabolism  in Salmonella , including those associated with the periplasmic nitrate reductase system, glucarate metabolism, the phosphotransferase system, cytochromes, and the succinate reductase complex in  S . Typhimurium in the mid-log growth phase, as well as those in the  ilv – leu  and histidine biosynthesis operons of intracellular  S . Typhimurium after invasion in Caco-2 cells. In the present study, we characterized the phenotypes and transcriptome effects of  speG  in  S . Typhimurium and reviewed the relevant literature to facilitate a more comprehensive understanding of the potential role of  speG  in the polyamine metabolism and virulence regulation of  Salmonella .

speG Is Required for Intracellular Replication of Salmonella in Various Human Cells and Affects Its Polyamine Metabolism and Global Transcriptomes