| Summary: | <i>Salmonella</i> <i>enterica serovar Typhimurium</i> (<i>S. Typhimurium</i>) is an important intracellular pathogen that poses a health threat to humans. This study tries to clarify the mechanism of <i>Salmonella</i> survival and reproduction in the host. In this study, high-throughput sequencing analysis was performed on RNA extracted from the strains isolated from infected mouse spleens and an <i>S. Typhimurium</i> reference strain (ATCC 14028) based on the BGISEQ-500 platform. A total of 1340 significant differentially expressed genes (DEGs) were screened. Functional annotation revealed DEGs associated with regulation, metabolism, transport and binding, pathogenesis, and motility. Through data mining and literature retrieval, 26 of the 58 upregulated DEGs (FPKM > 10) were not reported to be related to the adaptation to intracellular survival and were classified as candidate key genes (CKGs) for survival and proliferation in vivo. Our data contribute to our understanding of the mechanisms used by <i>Salmonella</i> to regulate virulence gene expression whilst replicating inside mammalian cells.
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