Salmonella enterica infections in humans may result in self-limiting gastroenteritis or in invasive systemic disease known as typhoid fever. Annually, S. enterica is responsible for causing as many as 430 million cases of gastroenteritis and typhoid disease, and the deaths of up to 950,000 people. Approximately 4% of patients infected with S. Typhi and 0.1% infected with non-typhoidal Salmonella (NTS) develop asymptomatic chronic carriage, becoming a reservoir for human disease and potential outbreaks. Despite decades of research, there remain significant gaps in our understanding of Salmonella infection, including the molecular mechanisms involved in establishing a chronic carrier state. Murine infection studies suggest that Salmonella form biofilms on cholesterol gallstones and these biofilms contributes to a chronic carriage state. This is supported by observations for infected patients where chronic carriage has been correlated with gallstone disease; currently the main treatment for chronic carriage is the removal of the gall bladder. We hypothesized that the Salmonella genes that confer the ability to chronically colonize the gall blabber must be conserved among Salmonella species and absent from other Enterobacteriaceae that do not effectively colonize the gall bladder. Bioinformatic analyses indicated the presence of such genes on the chromosomes of all Salmonella. Here we describe the characterisation of one such gene, we reveal the first tissue specific colonisation factor for Salmonella, we demonstrate a role in chronic colonisation of the host and provide a mechanistic understanding for persistence.