Molecular mechanisms of Salmonella virulence and host resistance

Salmonella species can cause typhoid fever and gastroenteritis in humans and pose a global threat to human health. In order to establish a successful infection, Salmonella utilize a large number of genes encoding a variety of virulence factors. Different animal models of infection have been used to better understand the mechanisms underlying each disease including cattle, rodents, and nematodes. To date, a number of different bacterial virulence factors have been identified using such animal models, most of which are secreted by two type three secretion systems (T3SS) encoded within Salmonella pathogenicity islands (SPI) 1 and 2. These proteins alter various host cell pathways, facilitating the invasion of epithelial cells during infection, as well as the survival and replication of Salmonella inside phagocytic cells. On the other hand, host genetics and resistance also play a role in the susceptibility to Salmonella infection. The natural resistance-associated macrophage protein 1 (Nramp1), for example, is critical for host defense, since mice lacking Nramp1 fail to control bacterial replication and succumb to low doses of S. Typhimurium. In this chapter, we analyze the different pathogen and host factors that play a role in the dynamic interaction between Salmonella and its host and their impact on disease.