Final Report Summary - ROLE OF SPIS (The role of Salmonella Pathogenicity Islands in salmonellosis outbreaks and invasive disease) Salmonella enterica is a facultative intracellular human and animal bacterial pathogen responsible for global pandemics of foodborne infections, posing a major threat to public health. This highly versatile pathogen can infect a broad range of hosts and causes different clinical outcomes. The single species S. enterica includes more than 2,600 serovars that share high sequence similarity and are taxonomically classified into six subspecies. Subspecies I serovars, adapted for mammals and avian hosts, are associated with more than 99% of all Salmonella infections in humans. The majority of non-typhoid Salmonella (NTS) infections in humans presents as gastroenteritis, however, about 5% may be invasive, and manifest as bacteremia or other extra-intestinal infections. Many of the NTS serovars are capable of colonizing the intestines of livestock with potential risk of contaminating the food chain and therefore, salmonellosis is often associated with animal products and produce. Many of the Salmonella virulence factors are encoded on mobile elements with variable presence between different serovars and even across isolates within the same serovar. Genomic diversity between related bacteria is largely determined by gain of functions via horizontal gene transfer (HGT). Mobile and integrative genetic elements, including plasmids, bacteriophages, transposons, integrons, integrative and conjugative elements (ICEs), and pathogenicity islands (PAIs) are very important vehicles of HGT enabling transmission of genetic information between bacteria. Horizontally acquired foreign DNA elements often encode genes that can profoundly affect the fitness, antimicrobial resistance (AMR) and the lifestyle of their bacterial host and therefore play a key role in bacterial evolution. Different projects in my lab are aimed to better understand on the molecular level, how differences between Salmonella serovars, or genetic variation between strains of a specific serovar affect Salmonella pathogenicity and host-pathogen interactions. Thanks to the generous support of the Marie Curie Reintegration Grant we were able to study the following projects:1. Genetic and phenotypic variation among non-typhoidal Salmonella serovars accounted for invasive disease in humans.2. Integrative analysis of Salmonella outbreaks and invasive salmonellosis in Israel.3. The epidemiology and molecular evolution of S. Infantis emergence in Israel.4. Molecular and Cellular Characterization of a Salmonella enterica Serovar Paratyphi A Outbreak Strain and the Human Immune Response to Infection.5. The role of the Salmonella enterica PhoP in regulation of Horizontally Acquired genes.During this time, the results of our research were presented in multiple national and international scientific conferences and published as five peer-reviewed papers in leading journals. Additional paper will be submitted in the very near future.