Neisseria gonorrhoeae causes about 800,000 new infections each year in the United States, with health-care costs approaching 2 billion dollars/year. Various surface components, including lipooligosaccharide (LOS) and opacity protein(s) (Opa(s)), are important in mediating disease. The objectives of this proposal are to understand how Opa and LOS function in disease, and determine if their interaction enhance virulence. The central hypothesis of the proposed research is that expression of specific Opa/LOS combinations promotes GC- GC interactions to produce biofilms with different disease potentiating properties and antibiotic resistance profiles. We intend to test our hypotheses by pursuing three specific aims: We will determine how Opa and LOS function cooperatively to promote bacterial-bacterial interactions, how bacterial-bacterial interactions effect the antibiotic resistance properties of GC biofilms and how bacterial aggregation influences adherence, invasion and/or transmigration. The results from our study will allow us to define how LOS and Opa variation contribute to disease pathogenesis. The impact on human health is expected to be significant, because with the new knowledge gained, we will be better positioned to understand what is needed to make a successful vaccine and what challenges we will face in developing new approaches to the treatment of gonorrhea.
Individually, Opa and LOS have been known to contribute to gonococcal disease in a variety of ways. However, their potential cooperative role in pathogenesis has not been studied. This proposal is designed to delineate the contributions of LOS and Opa cooperativity to disease.
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