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October 27, 2006
Promising Approach to Prevent Tooth Decay
Researchers 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
Targeting certain bacteria in the mouth is challenging because complex, multi-layered microbial communities called biofilms routinely form on our teeth. Biofilms are found in many parts of the body. While they aren't inherently a problem, they can protect harmful bacteria and play a role in several types of human infections.
Dr. Wenyuan Shi, a scientist at the University of California at Los Angeles School of Dentistry, and his colleagues set out to target the cavity-associated oral bacterium Steptococcus mutans Its one of at least 700 bacterial species, good and bad, that inhabit the mouth. Supported by NIH National Institute of Dental and Craniofacial Research among other organizations, they first tried attaching toxins to antibodies.Cancer researchers use such toxin-toting antibodies to kill tumor cells while leaving normal cells alone.
Despite some success in killing specific bacteria in the oral biofilm, the researchers soon encountered the same technical difficulty that cancer researchers ran into. Their targeting antibodies were large and bulky, making them unstable, therapeutically inefficient, and expensive to produce.
The researchers next looked through the complete DNA sequence of S. mutans and identified a small, 21-amino acid (the building blocks of protein) pheromone called CSP that they hoped would assure the toxin would find its target. They then used an automated machine to synthesize what they call a STAMP, for specifically targeted antimicrobial peptides. Like its postal namesake, STAMPs have a two-sided structure: a small anti-microbial bomb on one side linked to a homing sequence on the other.
The researchers described their results online on October 23, 2006, in the journal Antimicrobial Agents and Chemotherapy. After some trial and error, they were able to generate a STAMP using an eight-amino acid region of the CSP that still targeted S. mutans.When the stamp was applied to an oral biofilm grown in the laboratory from the pooled saliva of five people, it took only about 30 seconds to eliminate the S. mutans in the mixture while leaving the other bacteria intact.
Other scientists have succeeded in targeting specific bacteria in the laboratory before, but STAMPs are tiny by protein standards. They can be efficiently and rapidly produced by machines designed to synthesize small proteins.
We have already moved the S. mutans STAMP into human studies, where it can be applied as part of a paste or mouth rinse, Shi said. We are also developing other dental STAMPs that target the specific oral microbes involved in periodontal disease and possibly even halitosis.
Looking to the future, Shi said that new STAMPs against other potentially harmful bacterial species could potentially be generated in a matter of days.