The proposed research is concerned with the molecular population genetics of oral bacteria of the Streptococcus mutans complex, which is a primary etiological agent of human dental caries. Through the application of techniques of gel electrophoresis to a variety of enzymes extracted from single clones, the research will measure the extent and organization of allelic diversity at 20 to 30 structural gene loci in natural populations and in representative laboratory strains. The primary objective of the research is to study the multilocus genetic structure (including temporal variation) of populations of S. mutans in relation to the epidemiology of caries in order to determine whether high caries experience is associated with the occurrence of a specific subset of cariogenic strains, as assayed electrophoretically. The basic premise of the research is that multilocus electrophoretic analysis will provide the fine genetic resolution of strains that is required for epidemiological tracing and other research on populations of oral bacteria, and which is not provided by serotyping and other techniques currently in use. Baseline information on the total extent of genetic diversity in S. mutans and in related species of Streptococcus in the oral microflora will be obtained by analysis of existing clinical isolates that have already been characterized by DNA hybridization, serotyping, and bacteriocin assay. In longitudinal studies, genetic diversity among strains of S. mutans infecting individual human hosts and families will be measured and related to factors of age, sex, level of oral hygiene, and caries activity. Spatial segregation of strains in particular relation to carious lesions and sound tooth surfaces and temporal changes in the strain composition of the oral microflora within individual hosts will also be analyzed with respect to the etiology and epidemiology of caries. The proposed research will contribute to an understanding of the evolutionary relationships and species limits among strains of oral steptococci and to the development of a theory of bacterial population genetics.