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Case Western scientist studies natural antibiotics

Cleveland—Researchers from Case Western University may be on their way to inhibiting or preventing HIV from entering the body, stopping the bacteria that cause periodontal disease from infecting tissues in the mouth and helping wounds heal faster by preventing infection.

IMAGE: Dr. Aaron Weinberg, Ph.D.
Idea: Dr. Aaron Weinberg got the idea for his research while in dental practice, wondering how wounds in his patients' mouths healed so quickly.

These future accomplishments may be made possible by studying an agent isolated from common oral bacteria. The scientists, lead by Dr. Aaron Weinberg, Ph.D., professor and chair of the department of biological sciences and associate dean for research at the dental school, are looking at how human beta defensins—nature’s way of keeping oral microbes from invading the body and messing with a person’s health—can be used to create new treatments to block bacteria from entering through the epithelial linings on and in the body.

The five-year, $2.25 million National Institutes of Health-funded project continues the work of Dr. Weinberg, who began pondering the effects of bacteria and healing in the mouth when he was in dental practice. His patients would come in with wounds in their mouths that were either self-inflicted through biting their cheek or tongue or by burning their palates on hot food.

“I was intrigued at how quickly the wounds healed despite all of the bacteria in the mouth. It’s one of the dirtiest places in the body,” Dr. Weinberg said.

Dr. Weinberg began exploring this concept as an assistant professor in the periodontics department at the University of Washington in the mid 1990s. There, his group discovered there are common bacteria in the mouth that induce the expression and release of hBDs from oral epithelial cells that make up the lining of the mouth. HBDs, it turned out, kill bacteria, fungi and viruses.

Dr. Weinberg took his research agenda to Case Western, where his group isolated an agent from the oral bacterium Fusobacterium nucleatum that promotes the expression of hBDs. He coined the agent, FAD-I for Fusobacterium nucleatum-associated Beta-Defensin Inducer.

FAD-I was shown to induce the expression and release of the hBDs not only from oral epithelial cells but also from epithelial cells that make up the mucosal linings of other sites of the body, such as skin, the respiratory track and the gastrointestinal and urogenital tracks.

“It used to be thought that these linings were just barriers and all that microorganisms needed to do to cause disease was to get through the barriers. It now turns out that the barrier is alive and responds to challenges,” Dr. Weinberg said. “We started dissecting out the agent, trying to find out what is in this common organism that everyone has in their mouth that promotes the expression of these proteins.”

“Our goal is to eventually be able to protect linings of the body from microbial challenges better than the body is doing it now by using FAD-I to promote the expression of the defensin molecules in vulnerable mucosal sites,” Dr. Weinberg said. They have also found that the hBDs, once induced, are not only antimicrobial but also promote a beneficial immune response by recruiting specific white cells from the blood.

The idea is to promote the expression of nature’s own antibiotics in sites that would come into contact with FAD-I. That could involve injecting a treatment into a woman’s vaginal wall to protect her from contracting or spreading HIV through sexual contact; putting the agent into a gel or toothpaste or having a dentist insert it in the mouth to inhibit periodontal disease or gingivitis; or coating bandages so that a bruise or cut doesn’t get infected and heals faster, he said.

“Wouldn’t it be neat if we could promote the expression of Mother Nature’s own antibiotics in vulnerable sites by intentionally challenging the sites with FAD-I and thereby protecting the sites from microbial challenges?” Dr. Weinberg asked.

Dr. Weinberg is well-known for his work studying periodontal bacteria.