Researchers report initial success in promising approach to prevent tooth decay

Preventing cavities could one day involve the dental equivalent of a military surgical strike. A team of researchers supported by the National Institute of Dental and Craniofacial Research report they have created a new smart anti-microbial treatment that can be chemically programmed in the laboratory to seek out and kill a specific cavity-causing species of bacteria, leaving the good bacteria untouched.

The experimental treatment, reported online in the journal Antimicrobial Agents and Chemotherapy, is called a STAMP. The acronym stands for "specifically targeted antimicrobial peptides" and, like its postal namesake, STAMPs have a two-sided structure. The first is the short homing sequence of a pheromone, a signaling chemical that can be as unique as a fingerprint to a bacterium and assures the STAMP will find its target. The second is a small anti-microbial bomb that is chemically linked to the homing sequence and kills the bacterium upon delivery.

While scientists have succeeded in the past in targeting specific bacteria in the laboratory, this report is unique because of the STAMPs themselves. They generally consist of less than 25 amino acids, a relative pipsqueak compared to the bulky, bacteria-seeking antibodies that have fascinated scientists for years. Because of their streamlined design, STAMPs also can be efficiently and rapidly produced on automated solid-phase chemistry machines designed to synthesize small molecules under 100 amino acids, called peptides.

The first-generation STAMPs also proved extremely effective in the initial laboratory work. As reported in this month's paper, the scientists found they could eliminate the cavity-associated oral bacterium Steptococcus mutans within 30 seconds from an oral biofilm without any collateral damage to related but non pathogenic species attached nearby. Biofilms are complex, multi-layered microbial communities that routinely form on our teeth and organs throughout the body. According to one estimate, biofilms may be involved to varying degrees in up to 80 percent of human infections.

"We've already moved the S. mutans STAMP into human studies, where it can be applied as part of a paste or mouthrinse," said Dr. Wenyuan Shi, senior author on the paper and a scientist at the University of California at Los Angeles School of Dentistry. "We're also developing other dental STAMPs that target the specific oral microbes involved in periodontal disease and possibly even halitosis. Thereafter, we hope to pursue possible medical applications of this technology."

Shi said his group's work on a targeted dental therapy began about eight years ago with the recognition that everyday dental care had reached a crossroads. "The standard way to combat bacterial infections is through vaccination, antibiotics, and/or hygienic care," said Shi. "They represent three of the greatest public-health discoveries of the 20th century, but each has its limitations in the mouth. Take vaccination. We can generate antibodies in the blood against S. mutans. But in the mouth, where S. mutans lives and our innate immunity is much weaker, generating a strong immune response has been challenging."