Analysis of Campylobacter coli Lipooligosaccharide Core Diversity

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DESCRIPTION (provided by applicant): Campylobacter is the most important cause of gastroenteritis in the United States and a frequent cause of traveler's diarrhea in developing countries. A small but significant number of Campylobacter infections have also been linked to the development of Guillain Barre Syndrome (GBS). It is believed that GBS is triggered as a result of molecular mimicry between the sialic acid sugar residues on the outer core of the Campylobacter glycolipid, lipooligosaccharide (LOS) and the carbohydrate moiety of human gangliosides. LOS has been shown to be one of many virulence factors involved in important processes associated with Campylobacter-mediated infection and GBS. Little attention has been given for studies on the biosynthesis of the core oligosaccharide of LOS and its role in pathogenesis in the emerging food borne pathogen, Campylobacter coli. The broad, long term objective of this proposal is to further understand the assembly of the Campylobacter LOS and the role that structural diversity of the LOS, which exists among various Campylobacter species, plays in pathogenesis. Specific Aim I will focus on characterization of the LOS biosynthetic loci from C. coli Penner serostrains. Specific Aim II will focus on an analysis of C. coli LOS core oligosaccharide diversity among clinical isolates. Specific Aim III will focus on the genetic analysis of C. coli mutants involved in the biosynthesis of LOS. The specific aims in this proposal will be carried out utilizing experiments involving techniques of molecular biology and bacterial genetics that can be easily performed by both undergraduate and graduate student researchers. Furthermore, the studies in this proposal are expected to lead to the development of a more sensitive detection method of all C. coli serotypes present in clinical isolates and offer insights into the organization and function of the core oligosaccharide of LOS in the food borne pathogen, C. coli.