The complete nucleotide sequences of lacRABCDF and partial nucleotide sequence of lacE from the lactose operon of Streptococcus mutans are presented. (Mr 11,401), and 123 (NH2-terminal) amino acids, respectively. As inferred from their direct homology to the staphylococcal bc genes, these determinants would encode the repressor of the streptococcal lactose operon (LacR), galactose-6-phosphate isomerase (LacA and LacB), tagatose-6-phosphate kinase (LacC), tagatose-1,6-bisphosphate aldolase (LacD), and the sugar-specific components enzyme M-lactose (LacF) and enzyme U-lactose (LacE) of the S. mutans phosphoenolpyruvate-dependent phosphotransferase system. The nucleotide sequence encompassing the S. mutans lac promoter appears to contain repeat elements analogous to those of S. aureus, suggesting that repression and catabolite repression of the lactose operons may be similar in these organisms.Streptococcus mutans is known to attach to and colonize the tooth pellicle and peridontium of humans, where the utilization of dietary sucrose leads to the formation of dental plaque (20). The fermentative metabolism of these and other oral microorganisms yields lactic acid, which acts directly and indirectly upon the teeth and peridontium, ultimately causing caries and peridontal disease (12). The oral streptococci are also cariogenic in animal models when the diet contains acidogenic carbohydrates other than sucrose. These carbohydrates include lactose and starch, which are major constituents of the human diet, as well as less prevalent carbohydrates such as glucose, fructose, and maltose (18). Since lactose is present in high concentrations in bovine milk and is generally consumed by humans in large quantities throughout life, or at least during the preadolescent or "caries-prone" years, it can be considered a dietary carbohydrate of significant importance in cariogenesis. If the virulence of S. mutans is dependent upon its metabolic potential (12), it appears that a thorough understanding of not only sucrose but also lactose metabolism is essential before effective measures to eliminate dental caries in humans can be designed. Lactose catabolism by several oral streptococcal strains has been shown to proceed via two mechanistically distinct pathways. For some isolates, such as Streptococcus salivarius 25975 (22), the metabolism of lactose appears to proceed mainly by hydrolysis of the disaccharide via P-galactosidase to glucose and galactose (although significant lactose-phosphotransferase system [PTS] activity is induced upon growth on lactose). The latter hexose is then converted to glucose 6-phosphate via the Leloir pathway (29): D-galactose --D-galactose 1-phosphate -* D-glucose 1-phosphate -* D-glucose 6-phosphate. In S. mutans, low or negligible levels of 1-galactosidase activity are detectable (22). In this organism, galactose is phosphorylated during vectorial transport of galactose or lactose by the phosphoenolpyruvate-dependent PTS (13) and is then metabolized via the tagatose 6-phosphate pathway as described f...