Pathogenic bacteria have evolved complex mechanisms to cause infection and to evade the host immune system. The facultative intracellular pathogen Salmonella enterica is one such organism that has adapted a range of genes and pathways that enable host colonisation and persistence. S. enterica can be broadly be divided into two groups; serovars that are host specific and serovars that are generalists able to infect many different hosts. These different serovars often have specific genes that are important for survival in serovar specific replicative niches. However, one universal and important aspect of S. enterica infections is the ability of the infecting strain to cause chronic asymptomatic infections. It is estimated that up to 5% of people infection with S. enterica serovar Typhi become chronically infected, and there are examples of chronic carriers in other human, pig, chicken and mouse infections with Salmonella. We hypothesized that the genes required for the development of chronic Salmonella infections would be highly conserved. Using a bioinformatics approach, we identified conserved Salmonella genes that are not present in other closely related Enterobacteriaceae. From our list of conserved genes, we identified genes that were present on specific Salmonella pathogenicity islands, and those that encoded for known virulence factors, such as type three secretions system apparatus and effectors. We also identified genes of unknown biological function that had not been linked to Salmonella virulence. Here, through a combination of molecular in vivo, omics and enzymatic techniques, we demonstrate a tissue-specific role for one such gene and provide evidence that it is important during Salmonella chronic infections.