A team of researchers from the University of California, Los Angeles School of Dentistry report they have created an antimicrobial treatment that can be chemically programmed in the laboratory to seek out and kill Streptococcus mutans, while leaving nonpathogenic bacteria untouched.
The experimental treatment, called a "STAMP," is reported in the November issue of Antimicrobial Agents and Chemotherapy. The acronym stands for "specifically targeted antimicrobial peptides" and, like their 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 ensures that the STAMP will find its target. The second is a small antimicrobial bomb that is linked chemically to the homing sequence and kills the bacterium on delivery.
While scientists previously had targeted specific bacteria in the laboratory, this finding is unique because of the STAMPs themselves. They generally consist of fewer than 25 amino acids, which is quite small compared with the bulky, bacteria-seeking antibodies that have interested scientists for years. Because of their streamlined design, STAMPs also can be produced efficiently and rapidly on automated solid-phase chemistry machines designed to synthesize small molecules of fewer than 100 amino acids, called "peptides."
"We’ve already moved the S. mutans STAMP into human studies, where it can be applied as part of a paste or mouth-rinse," said Wenyuan Shi, PhD, senior author of the report and a scientist at the UCLA 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."
Randal Eckert, PhD, a UCLA scientist and the lead author on the study, explained that the researchers turned to an online database that contains the complete DNA sequence of S. mutans. They identified a 21-peptide pheromone called "competence stimulating peptide" (CSP) that was specific to the bacterium. From there, they typed instructions into an automated solid-phase chemistry machine to synthesize at once the full-length CSP and a 16-peptide antimicrobial sequence. The outcome was the first batch of STAMPs.
After some trial and error, the scientists ultimately generated a STAMP with the same antimicrobial agent but with a signature eight-peptide CSP sequence to target S. mutans. "We pooled saliva from five people and created an oral biofilm in the laboratory that included a couple hundred species of bacteria," said Dr. Eckert. "We applied the STAMP, and it took only about 30 seconds to eliminate the S. mutans in the mixture, while leaving the other bacteria intact."
The National Institute of Dental and Craniofacial Research, National Institutes of Health, supported the research.
