An analysis of the role of glucan-binding proteins in Streptococcus mutans biofilm architecture and caries development

Tooth decay is a serious health risk and a significant contributor to health care costs in both industrialized and developing nations. Tooth decay is the end result of a change in the balance of plaque ecology towards more acidogenic and aciduric bacterial species. Frequent and prolonged periods of low plaque pH, facilitated by the presence of fermentable simple carbohydrates drive the cycles of enamel homeostasis towards demineralization and ultimately dental caries. Streptococcus mutans is the main etiologic agent in the development of dental caries. Their cariogenic potential is based on the ability to produce and tolerate large amounts of acid and to adhere to and accumulate large numbers on the surface of a tooth. They are capable of efficiently fermenting a variety of simple carbohydrates and can produce high concentrations of acid, even in a low pH environment. However, it is the ability of S. mutans to rapidly synthesize copious amounts of water-insoluble and water-soluble glucan from dietary sucrose, which allow the bacteria to accumulate large enough numbers to dominate the dental plaque and significantly lower the plaque pH. Synthesis of glucan is mediated by glucosyltransferase enzymes and is crucial to sucrose-dependent adherence and to the cariogenicity of S. mutans. S. mutans also makes four non-GTF glucan-binding proteins: GbpA and GbpD contain a region that is homologous to the glucan-binding domains of the Gtf enzymes, and GbpC confers the property of dextran-dependent aggregation during stressful conditions, and GbpB whose glucan-binding properties appear secondary to its role in cell-wall metabolism. It was hypothesized that Gbps A, C, and D shape the architecture of S. mutans biofilms which in turn affects the cariogenicity of S. mutans. To test this hypothesis, a panel of Gbp mutants was constructed from S. mutans strain