LIPOOLIGOSACCHARIDE BIOSYNTHESIS IN NEISSERIACEAE

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The ongoing epidemic of gonorrhea has made Neisseria zonorrhoeae one of the most important human pathogens. The total health care costs of the disease exceeds 1 billion dollars per year. A closely related pathogen, N. Meningitides, has a mortality rate of approximately 85% when left untreated, but can be less than 1% when vigorous antibiotic and support therapy is administered early. A wide variety of cell surfaces polymers have been implicated as virulence factors, and yet little is known of the pathogenesis of the two diseases. Lipooligosaccharides may be the most important surface antigen, with respect to adherence and susceptibility of the organism to the killing action of normal human serum. The work to be described in this proposal demonstrates how state of the art molecular biology techniques can be used to study lipooligosaccharide biosynthesis in these pathogens. The genes involved in the biosynthesis of the polysaccharide portion of this molecule will be identified by molecular cloning and reactivity with monoclonal antibodies. Mutants that no longer produce this lipooligosaccharide will be constructed. These strains will be used to elucidate the genetic basis of lipooligosaccharide biosynthesis.