Research from Case Western Reserve University School of Dental Medicine to study an isolated agent from common oral bacteria may hold the answer as to how human beta defensins (HBDs)—nature’s way of keeping oral microbes from entering the body and wreaking havoc on our health—can be used to create new treatments to block bacteria from entering through the epithelial linings on and in the body.
Aaron Weinberg, professor and chair of the Department of Biological Sciences at the dental school, will lead the research group on a five-year, $2.25 million National Institutes of Health-funded project.
The new grant, Weinberg said, will continue the exploration of their discovery last year of an agent called Fusobacterium nucleatum-associated Beta-Defensin Inducer (FAD-I).
This agent triggers the expression and release of the HBD peptides from epithelial cells that make up the mucosal linings of the body, such as skin, the respiratory track and the gastrointestinal and urogenital tracks.
Weinberg and his research group reported FAD-I’s discovery in the Journal of Biological Chemistry article, “Fusobacterium nucleatum-Associated Beta-Defensin Inducer (FAD-I).” The researchers described the identification, isolation and functions of FAD-I.
The new grant that continues FAD-I research has several focuses: (1) isolating which strains of F. nucleatum bacteria have more potent FAD-I activity and why, (2) continued research to understand more about the biology and structure of FAD-I, and (3) using a mouse model to see how effective it is as a potential treatment.
In addition, the researchers are particularly interested in why FAD-I sets defensins to work without triggering inflammation, which can be a health risk if the inflammation is not abated by the normal defense system. In the mouth, it can cause gum disease and eventual tooth loss.
“It started with our observation that when the bacterium comes in contact with human epithelial cells, it promotes the induction of these HBD peptides,” Weinberg said.
HBDs put up a defense when challenged by oral bacteria and block the invasion of the more than 700 species of bacteria in the mouth from entering the body. Oral bacteria have been linked to pre-term labor, fetal death, heart disease, diabetes and other health conditions.
The researcher and his team have studied the link between the mouth’s bacteria and the induction of HBDs for more than a decade, and in a step-by-step process have unraveled the symbiotic relationship between this common oral bacterium and the peptides.
In the process of understanding HBDs and oral bacteria by focusing on F. nucleatum, they discovered FAD-I on the surface of the outer membrane of this bacterium. Even when the outer membrane portion containing FAD-I was separated from the main bacterium, FAD-I continued to induce HBD action in vitro. In addition, when researchers genetically expressed FAD-I in other bacteria that didn’t induce HBD expression and release from epithelial cells, the bacteria were then able to induce HBD expression and release, Weinberg explained.
So, the idea is to promote nature’s own antibiotics in sites where they would come in contact with FAD-I, Weinberg said.
“The possibility exists that FAD-I can induce defensins in other parts of the body where they are found. 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?”