The goal of this study is to elucidate the structure, function and vaccine potential of two related 44,000 dalton (44kDa) proteins of Neisseria gonorrhoea. The inter-related hypotheses to be tested are: that a surface- exposed and a periplasmic 44kDa protein are similar proteins that are encoded by separate but related genes; that the 44kDa proteins are gonococcal homologies of clongation factor Tu; and that the surface- exposed 44kDa protein is a potential vaccine candidate. The proposed model is that the periplasmic 44kDa protein is the gonococcal homologue of elongation factor TuA (EFTuA). The surface-exposed 44kDa protein appears to be modified with lipid and/or carbohydrate components of peptidoglycan which may result in the protein being inserted into the outer membrane. Because EFTuB of Escherichia coli has been shown to associate with membranes, the exposed 44kDa protein may be the gonococcal homologue of EFTuB. Other properties, such as peptidoglycan association and penicillin-binding activity, has been associated with the 44kDa proteins. Because the surface-exposed 44kDa protein is constitutively and universally expressed and structurally conserved among gonococcal strains, and has similar surface-exposure in four test strains, Dr. Judd proposes that it may contain stable epitopes suitable for use in a vaccine. The objective of this study is to structurally, functionally, and immunologically characterize the exposed and periplasmic 44kDa proteins through the following aims: 1) cloning and sequencing of the genes for the 44kDa proteins; 2) generation of deletion mutants lacking the genes coding for the 44kDa proteins; definition of the cellular location of the 44kDa proteins and characterization of possible modification(s) with lipid and/or peptidoglycan components; and 3) analysis of the antibacterial activity of monoclonal and nonspecific polyclonal 44kDa antibodies.
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