June 4, 2015

Targeted bacteria-killer offers promise in fighting tooth decay, other diseases

A new treatment that can kill the bacteria responsible for tooth decay without harming the mouth’s beneficial bacteria has moved one step closer to reality with a study by researchers at the University of Washington and UCLA.

The study, published in the June issue of the Proceedings of the National Academy of Sciences, shows how a specifically targeted antimicrobial peptide, or STAMP, known as C16G2 eradicates harmful acid-producing Streptococcus mutans bacteria without killing benign bacteria.

A Streptococcus mutans bacterium is shown before (left) and after treatment with the C16G2 specifically targeted antimicrobial peptide.

A Streptococcus mutans bacterium is shown before (left) and after treatment with the C16G2 specifically targeted antimicrobial peptide. Dr. Wenyuan Shi/UCLA School of Dentistry

 

The finding is a critical advance because, as scientists have understood for about two decades, the vast majority of bacterial cells in the human mouth are not harmful. However, most common broad-spectrum antibiotics and conventional mouthwashes indiscriminately kill both beneficial and harmful bacteria, and their effects last for only about 12 hours.

In addition, overusing broad-spectrum antibiotics can not only increase bacterial resistance, but also seriously disrupt the body’s ecological balance, which can make people more susceptible to microbial infections. As a result, there is no effective treatment for bacteria-induced tooth decay. While fluoride has been an effective weapon against tooth decay, it works by strengthening tooth enamel rather than attacking the Streptococcus mutans bacteria, which convert sucrose to lactic acid that attacks the teeth.

The STAMP approach, on the other hand, restructures the mouth’s microbiome, or microorganism population, to produce an environment that supports better oral health. Moreover, the STAMP approach could possibly be used against other microbiome-related diseases, meaning it could have an impact far beyond dentistry, said Dr. Dr. Wenyuan Shi, the study’s lead author and chair of the section of oral biology at the UCLA School of Dentistry.

Dr. Jeffrey McLean

Dr. Jeffrey McLean

A growing number of studies have linked  changes in the composition of the human microbiome to numerous disease states. When bacteria cause diseases, it is typically because they grow beyond their normal population size or niche (which can occur when the body’s immune system is compromised), or because microbes enter parts of the body that are normally sterile, such as the blood, lower respiratory tract or abdominal cavity.

“This is a truly momentous discovery that provides proof-of-concept on re-engineering human microbiome for treatment and prevention of diseases,” Dr. Shi said. “It demonstrates that this targeted approach actually works and that it is an incredibly powerful tool that can be used to manipulate our microbiomes.”

The researchers’ latest work builds on earlier studies that led Dr. Shi to develop an experimental STAMP mouthwash in 2011. The new study shows that the STAMP, in addition to eradicating  Streptococcus mutans, also increased the abundance of  other Streptococcus species that are highly prevalent in healthy oral cavities, including one that is strongly linked with healthy dental plaque.

Study co-author Dr. Jeffrey McLean of the University of Washington School of Dentistry said, “Targeted killing of individual species that can trigger or significantly advance disease within our delicately poised microbiome is crucial to keep the entire system in balance. Importantly, this study also represents a major step towards understanding how that balance may be shifted towards a healthy state after removing a single disruptive member of the human microbiome community.”

The C16G2 STAMP is now delivered via a gel tray, which the researchers have chosen as a more promising vehicle than the mouthwash. It is being developed for use in preventing tooth decay and cavities under an investigational new drug application with the U.S. Food and Drug Administration by Los Angeles-based C3 Jian, a company Dr. Shi founded around patent rights he developed at UCLA. It is currently in Phase 2 clinical trials.

Dr. John Mekalanos, chair of microbiology and molecular genetics at Harvard Medical School, and the article’s editor, said, “The challenge of trying to modulate the abundance of a single member of our complex microbiota is enormous. Dr. Shi and his colleagues have provided an exciting new way to do just that.”

The study’s other main authors include Dr. Xuesong He of UCLA Dentistry and Brian Varnum of C3 Jian. The study was supported by the National Institutes of Health and by C3 Jian.