Environmental factors can affect the composition of Neisseria gonorrhoeae. It is likely that any effective gonorrhea vaccine will consist of one or more cell surface components. Therefore, we believe it is important to define the composition of the gonococcal cell envelope and to determine how it varies with respect to environmental conditions. The cell envelope is also involved in the interaction of the gonococcus with the human host. Changes in the composition of the cell envelope can affect this interaction. We hope to identify cell surface components that are required for growth and survival under in vivo conditions. In addition, the results of these studies will further our understanding of the pathobiology of gonococcal infections. We will approach the potential effects of the environment by growing gonococci under various conditions in continuous culture. During continuous culture, the environment is constant and the composition of the organism is determined by the specific growth parameters. Thus, we will be able to observe whether any changes occur in the lipopolysaccharide, outer membrane proteins, cell surface hydrophobicity, serum resistance, and other factors implicated in virulence. In addition, we will examine the effect of specific genetic loci on the antigenic structure of lipopolysaccharide and its relationship to serum resistance. We will also investigate the factors responsible for the serotype variability of the lipopolysaccharide. Other studies will investigate the specificity of opsonic antibodies to gonococcal cell surface components and their relationship to various clinical syndromes. We will also determine when protein I-specific opsonic antibodies are acquired by normal individuals. Another aspect of our studies on the effect of environmental conditions concerns the proteins produced by gonococci grown under iron-limiting conditions, a factor which occurs during in vivo growth. These proteins will be studied with respect to their structure, function, how and when they are produced and their distribution among diverse gonococcal strains. With respect to function, we will use recombinant DNA techniques to obtain mutants that are defective in one or more of these proteins. In this way, we hope to determine whether specific proteins are required for in vivo growth.
