Identifying the contribution of the prevalent, diverse, phage-derived gtr operons to O-antigen modification and Salmonella diversity, virulence and persistence. (360G-Wellcome-094333_Z_10_Z)

Salmonella enterica enterica serovars Typhimurium and Enteritidis are a major cause of gastroenteritis but a specific Typhimurium strain lineage is associated with systemic disease. Strain evolution by genome degradation and horizontal gene transfer is ongoing. This application focuses on a diverse group of glycosyltransferase (gtr) operons that are phage derived or encoded, and of which individual Salmonella genomes can encode multiple variants. Our hypothesis is that these gtr operons med iate significant diversity in immunodominant antigens of Salmonella, specifically of the O-antigen or capsule. This could facilitate co-infection in animal reservoirs and thus persistence, and may directly enhance virulence. The overall goal of the project is to further our understanding of the role and significance of the gtr operons. Our three Specific Aims are to determine signals occurring during infection that alter gtr expression, to identify the biochemical activity of members of differ ent and diverse gtrC families, and to assess the role of the gene products in host-pathogen interactions. This builds upon current work that identified phase variation as a common gtr regulatory mechanism and novel O-antigen gtr mediated changes. A better understanding of gtr-mediated modification may contribute to the development of improved tools for epidemiology and vaccines.