The immunodominant O-antigen and Salmonella enterica pathogenesis: examining the phage origin, distribution, expression and role of a family of O-antigen modification gene clusters. (360G-Wellcome-080086_Z_06_Z)

The bacterial species Salmonella enterica causes typhoid fever and is a major cause of gastroenteritis, or food poisoning, leading to significant costs and health concerns in humans and livestock worldwide. To develop approaches to combat this problem, it is important to identify immunogenic antigens and to determine when these are expressed. This application focuses on the immunodominant O-antigen of the lipopolysaccharide and the diversity of O-antigen modification, specifically glycoslyation encoded by gtr gene clusters. Our hypothesis is that co-existence of different isolates from the same serogroup is facilitated by phase variation of gtr genes and that phage facilitate horizontal distribution of these genes, which together will influence the persistence and spread of this species in the animal hosts. Our Specific Aims are to characterize regulation of gtr expression, and to determine the presence of gtr among serovars and identify linkage with phage related sequences. In selected isolates the biochemical nature of the modification will be characterized and possible effects on type III dependent secretion examined. A better understanding of O-antigen modification in S. enterica can contribute to the development of improved tools for epidemiology and vaccines, and enhance our understanding of the virulence mechanisms of this important pathogen.