The research will concentrate on the genetics and mechanisms of antibiotic resistance in the gonococcus, and on the genetic and biochemical basis for virulence. Existing mutations which probably affect the permeability of the outer cell membrane will be chemically characterized, and these mutants will be studied for alterations in virulence by several techniques (animal models, sensitivity to antibody plus complement, others). Other mutants which affect virulence will be sought, with the particular goal of dissociating colony type/virulence/competence in genetic transformation. Attempts will be made to construct meningococcal/gonococcal hybrids, with the goal of introducing into the gonococcus meningococcal genes for production of immunogenic polysaccharide capsule; if successful, the virulence and animal-host response to the hybrids will be studied. Auxotrophic mutants will be selected, one use of which will be more precise mapping of the many loci affecting antibiotic resistance. The kinds and functional role of plasmids will be further defined. The linked genes near str...spc will be studied to document whether this is a large cluster of ribosomal genes.