Replacement Therapy for the Prevention of Dental Caries

Objectives: Despite traditional and innovative prevention methods, dental caries remains the most prevalent chronic infectious disease of humans. We have developed a novel method for prevention called Replacement Therapy in which a Streptococcus mutans strain has been tailored using recombinant DNA technology to create a strain that does not cause disease and can protect the host from disease-causing strains of this pathogen. Methods: a chance observation led to the discovery that mutating the gene for lactate dehydrogenase resulted in an S. mutans mutant that was non-cariogenic. We then investigated phenotypic properties that might provide an advantage to colonization. We discovered a strain that produced an antibiotic capable of killing all other S. mutans strains. Recombinant DNA methods allowed us to combine lactate dehydrogenase deficiency with antibiotic production into a single effector strain called SMaRT. This strain has been extensively tested for its ability to serve as a replacement strain in the prevention of caries. Results: SMaRT has very little cariogenic potential and it does not upset the normal oral microbial ecology. The antibiotic allows SMaRT to preemptively colonize the S. mutans niche on the tooth surface. In human trials, a single 3 minute application of a prototype strain resulted in persistent colonization. No adverse side effects were observed in acute and chronic toxicity studies. The genetic alterations in SMaRT are extremely stable. Conclusions: SMaRT replacement therapy appears to be well suited for use in prevention of caries. Because the strain is virtually identical to S. mutans present in most people's mouths, there is minimal risk associated with this technology. A single 5 minute treatment is expected to provide lifelong protection against caries and is not dependent on patient compliance. As a result, SMaRT is anticipated to have a significant impact on the incidence of dental caries in the human population.