Our long-term goal is to understand the process by which Salmonella adapts to a broad range of hosts i.e. becomes a generalist Salmonella strain. We will determine the molecular mechanisms which allow pathogens such as S. Enteritidis to invade and infect humans and a wide range of food-producing animals, including mammals and birds. Host adaptation of Salmonella appears to be a much more complex process than anticipated so far. We hypothesize that it occurs simultaneously at numerous sites in the Salmonella genome, involving changes in genes that encode receptors, colonization factors, porins and other outer membrane proteins. Further, we hypothesize that the long process through which a Salmonella strain becomes a generalist occurs through genomic degradation or genomic augmentation. We propose to test these hypotheses through the following two Specific Aims:Specific Aim 1: to identify host-associated nsSNPs in the protein coding regions of antigenic genes and determine the presence and absence of coding genes in S. Enteritidis strains adapted to human or avian hosts.Specific Aim 2: to determine the role of the T169A nsSNP in the FimA adhesin of avian-adapted S. Enteritidis.