LIPOOLIGOSACCHARIDE BIOSYNTHESIS IN NEISSERIACEAE

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Description (adapted from the applicant's abstract): Neisseria gonorrhoeae is responsible for over 1 million cases of gonorrhea each year in the United States and the total health care costs associated with treating gonorrhea, and complications that arise from infections caused by this organism exceed 1 billion dollars per year. An effective vaccine would dramatically reduce the associated health care costs. This proposal focuses on elucidating the genetic mechanisms responsible for the expression of one of the organism's principal surface antigens, lipooligosaccharide (LOS). In the work to be described, I will identify by gene cloning and genetic complementation techniques, genes required for the LOS biosynthesis. I will characterize these genes by DNA sequence analysis, define the biochemical properties of the gene products and determine their role in the biosynthetic process. Since the gonococcus can vary its LOS, depending on the host and the local environment, studies on the genetic regulation of its synthesis are warranted. Stable LOS-producing strains are needed to allow us to dissect the role of LOS in the disease process. I will construct a series of genetically defined LOS mutants that express defined LOS structures. These strains will also allow us to study the interaction of the expression of this molecule with other cell surface components. Understanding how the expression of LOS is regulated will allow us to design experiments to test the role of each cell surface component in the disease process. By understanding the relationship between disease and the expression of a specific surface component, we can design vaccines that can prevent the disease in specific demographic groups.