LIPOOLIGOSACCHARIDE BIOSYNTHESIS IN NEISSERIACEAE

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.