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Salmonella enterica is a leading cause of bacterial food-borne disease that affects more than 1 million people in the United States and more than 90 million people world-wide each year. Infection causes febrile diarrheal disease in most people. In addition to diarrheal disease, Salmonella causes the most deaths of any food-borne pathogen in the US and is a leading cause of death of children and immunosuppressed people worldwide. As a food-borne pathogen, contaminated food and water are the major cause of disease outbreaks in people. In addition to its impact on human health, Salmonella also causes diarrhea and sepsis in mammals, leading to significant impact on animal welfare. Therefore, it is imperative to understand how Salmonella thrives in infected hosts and in the environment to eradicate this zoonotic pathogen.