Non-typhoid Salmonella (NTS) enterica is a major cause of foodborne infections in industrialized countries and a leading cause of hospitalization and death among bacterial foodborne pathogens. The vast majority of the Salmonella virulence factors are encoded within horizontally acquired discrete regions along the chromosome known as Salmonella Pathogenicity Islands (SPIs). SPIs are crucial for Salmonella virulence. Herein we propose to study the role of 17 SPIs and associated virulence loci in different aspects of NTS pathogenicity including the ability to cause outbreaks, host-to-host transmission, and manifestation of invasive disease. In the first stage of the study we will map and characterize the distribution of these virulence loci across various outbreak and bacteremia isolates. This analysis will provide a broad view over the distribution of SPIs in highly virulence isolates, which are clinically relevant in Israel and Europe. Based the collected data, we will develop a Quantitative Microbial Risk Assessment approach for detection of virulent Salmonella strains in food, environmental and livestock samples. In addition we are interested in investigating the potential contribution of SPIs to the oral-fecal route of transmission. To do so, we will use the persistent mouse model and study the ability of Salmonella strains, harboring SPIs deletions to transmit the disease over time. The gained data are expected to yield a broader understanding about the role of primary virulence loci in the pathogenesis and epidemiology of Salmonella and will shed light on the evolution of pathogenic Salmonella serotypes. Understanding these mechanisms will contribute to our knowledge about host-pathogen interactions and the molecular basis of outbreaks. Deeper understanding about these processes could lead to better prevention and treatment of infectious diseases and may provide new therapeutic targets for the development of novel antimicrobial chemotherapies and vaccines.