Prior to 1972, the genetic analysis of the human opportunistic pathogen, Staphylococcus aureus, was conducted almost exclusively by generalized transduction, a technique which suffers several inherent limitations. With the demonstration of reproducible transformation (and transfection) among the 8325 strains of S. aureus in 1972, the opportunity for significant advances in this area was apparent. Results obtained in this laboratory have shown that transformation offers an excellent means for characterizing the chromosome map of S. aureus, and work in this area has begun. More recent results from our work have shown that competence for transformation arises in response to the surface adsorption of phage belonging to serological group B, and that the ability to become competent is a potential of virtually all strains of S. aureus. This proposed research is therefore directed towards the following major objectives: (1) To further the genetic characterization of the linkage map which constitutes the chromosome of S. aureus, to identify wherever possible the sites of plasmid, prophage, and translocation sequence integration, and to examine the evolutionary relationships between "chromosomal" and plasmid-borne genetic determinants; (2) to further characterize the interaction between phage and host cell that leads to competence for transformation; and (3) to assess the taxonomic relationships which may exist among various members of the species S. aureus and between members of this and other species thought to be related (notably S. epidermidis). This study, and the foregoing objectives, represent a logical extension of a long-term study of the genetics and biochemistry of S. aureus. Emphasis is placed on the relationships which exist between normal cellular metabolism and structure, and clinically significant characteristics that bear directly or indirectly on pathogenicity, antibiotic resistance, and epidemiology.