NJDS Researcher's Discovery
by Eve Jacobs

Jeffrey Kaplan’s modest demeanor and quiet manner are certainly not indicative of his recent major coup. Fortunately, the NIH has no reservations about singing his praises publicly and often. The UMDNJ-New Jersey Dental School (NJDS) researcher has been credited by the NIH with one of its top six science discoveries nationwide this year.

As in much of science, the path to this discovery was neither arrow-straight nor anticipated. In fact, Kaplan, an associate professor in the NJDS Department of Oral Biology, was studying one bacterium when he unearthed critical information concerning another.

The story goes something like this. Kaplan was studying Actinobacillus actinomycetemcomitans (Aa), an oral bacterium with a difficult-to-pronounce name, involved in severe periodontal disease. Aa has been the object of intense study for years by researchers in the oral biology laboratories of NJDS, headed up by Daniel Fine, DMD, professor and director of the lab, and a renowned expert in this field.

Kaplan and co-investigators at the school had previously found that Aa spreads out when cultured in the laboratory. At first, the scientists were perplexed by this spreading motion, since the bacterium is not capable of moving independently.  But soon they discovered that Aa release themselves from the surface of the
culture dishes and diffuse outwards by secreting a previously unknown enzyme, which the researchers named dispersin B [based on the word disperse].

In line with their role as biochemical catalysts, all enzymes demonstrate considerable selectivity for the molecules upon which they act. Some enzymes demonstrate absolute specificity, reacting with only one molecule; many react with a small group of closely related chemical compounds.

Because enzymes target specific molecules, the NJDS researchers set about finding the target molecules for dispersin B. They already knew that the enzyme acts on polysaccharides (long sugar chains), but they did not know which ones, so they turned to a large online database that includes genome sequences of human pathogens. Here they were able to identify one target: long sugar molecules made by Staphylococcus epidermidis, an organism normally found on skin that is known to contaminate indwelling medical devices.

These bacteria infect catheters and other medical devices by producing a sticky layer called a biofilm, which allows them to attach firmly to the instrument. There, the bacteria often multiply rapidly and can then spread to adjacent organs, such as from a urinary catheter to the bladder. Staph epidermidis is a frequent contaminant of medical devices, costing the healthcare system billions of dollars each year.

In further studies, the researchers demonstrated that when dispersin B is coated on catheters, it works to prevent biofilm formation. Also, the enzyme can detach already established biofilms by interfering with their attachment and/or consequently making the bacteria more sensitive to conventional antibiotic therapy.

The dental research team also showed that the dispersin B coating is a practical solution to the biofilm problem, since it lasts at least one month and shows no signs of breaking down. This makes it possible to store coated catheters until they are needed.

“What is exciting is that by doing basic research on this oral bacterium Aa, we discovered an enzyme that may have potential use as an antibacterial agent in the clinic,” says Kaplan.

Dispersin B may also be effective in preventing and dispersing biofilms formed by Staphylococcus aureus and Escherichia coli, also among the most common causes of infections associated with indwelling medical devices.

Looking to the future, Kaplan says the enzyme could be used as an anti-biofilm agent in various ways. Although Staph epidermidis is usually not very aggressive, it is resistant to many antibiotics and can lead to persistent infections. The bacteria can multiply and end up in the bloodstream, sometimes leading to severe
infections and even death, particularly in immunocompromised patients. More than 10,000 people each year die as a result of catheter-related bloodstream infections.

This discovery is likely to leap from “bench to bedside” in an unusually short period of time. The article detailing the findings, entitled “Enzymatic Detachment of Staphylococcus epidermidis Biofilms,” was published in Antimicrobial Agents and Chemotherapy in July 2004. Dispersin B has already been licensed for manufacture to Kane Biotech Inc.

Collaborating with Kaplan were Drs. Chandran Ragunath, Kabilan Velliyagounder, Daniel H. Fine, and Narayanan Ramasubbu of the NJDS Department of Oral Biology. The work was supported by the National Institute of Dental and Craniofacial Research.