Small Beginnings, Big Outcomes
words by Merry Sue Baum / photograph by Andrew Hanenberg
effrey Kaplan, PhD, knows first hand that focusing on little things — very little things — can have a huge impact. As a child, he encountered an ant that sparked his love of science. Today, his study of microorganisms has led to a discovery that may make certain types of infections a thing of the past.
Then he was about 10, Kaplan recalls, he was at a backyard picnic and decided to put a potato chip in the path of an ant and see what would transpire. The insect crawled around and over the chip, then went into a crack in the sidewalk. It soon resurfaced, but crawled into another nearby crack. Even though it had disappeared twice, young Jeff patiently waited. Eventually a long trail of ants emerged, presumably led by the “scout,” and marched, in perfect formation, directly to the chip. The little workers broke it apart and carried it, bit-by-bit, back down into the crack.
“I watched the whole thing for hours, I was so captivated,” Kaplan recalls. “This tiny creature sensed a food source and recruited others to help him take it to the nest. I wondered how he communicated what was happening and where. That’s when I fell in love with science.” He went on to earn a BS in biology and a PhD in molecular biology at the University of Illinois, in his hometown of Chicago. “I enjoy biology more than physics or chemistry, because those sciences are somewhat predictable,” he says. “With biology, Mother Nature is always throwing you a curveball.”
It was just such a curveball that led Kaplan to a discovery that may result in a new treatment for virulent infections. It began when he was working in the lab of Daniel Fine, another NJDS researcher, with a bacterium known as Aggregatibacter actinomycetemcomitans, or Aa. Found in the oral cavity, Aa forms a biofilm, or slimy matrix, that enables it to stick to surfaces. The resulting plaque is responsible for causing dental caries and periodontitis, or gum disease. When Kaplan cultured Aa to see its characteristics, he noticed it produced comet-like streamers of satellite colonies. He wondered if Aa might reproduce like sessiles, immovable organisms that replicate by scattering their seeds. “Some sessiles use burrs to reproduce, for example, and some fungi form little sacs that forcefully shoot out seeds, almost like a little explosion,” he explains. “I thought that’s what I might be seeing, an Aa biofilm that was dispersing.”
The molecular biologist began searching for research being done on biofilm dispersal, but came up empty. “Scientists were looking at how biofilms attach to surfaces and how they form the slimy matrix that holds them in place,” he says. “But no one was looking at methods of dispersion.” He decided to be the first. He took an approach commonly used in microbiology when studying a process: He created an Aa mutant that did not disperse and worked with individual genes to see which were involved in the process. That’s when he discovered dispersin B, an enzyme that breaks down the slime layer of Aa. “We knew immediately that it had the potential for clinical applications, because biofilms are a tough problem,” he says. “It made sense that if we could use the enzyme to dissolve the slimy matrix, it might make treating the bacterial infection easier.”
That was in 2003. By 2005, dispersin B was patented and is now licensed to Kane Biotech, Inc. in Winnipeg, Canada, which has manufactured it in the form of a topical wound gel. It is currently undergoing final FDA-recommended testing, and Kane expects to submit an application to the FDA to start clinical trials this summer. “Because it’s not ingested or injected, the FDA considers dispersin B a medical device, not a drug,” says Kaplan. “That makes it easier to get approval.” Along with clinical trials, the wound gel may be used with a patient’s permission as a last resort, when all other treatments have failed. An example of this “compassionate care” use, as it is known, is treating a diabetic who must have a foot amputated because of an ulcer that will not heal.
Once the wound gel is shown to be safe and effective, other applications with dispersin B will be tried. In the course of his investigation, Kaplan found that the enzyme is effective against a number of other biofilms, including that of Staphylococcus epidermidis. Staph is a bacterium responsible for many hospital-acquired infections, including those that occur in catheters and implanted medical devices like heart valves and artificial joints. Dispersin B may eventually be used as a coating and a pre-rinse for medical devices and as an antiseptic and pre-surgical rinse. Even though every precaution is taken and physicians work under totally sterile conditions, about 5 percent of all surgical wounds get infected.
“We expect dispersin B will reduce the incidence of these infections,” Kaplan says. “There is also recent data that suggests the enzyme might even be effective in treating acne.”
Besides helping quell human infections, Kaplan’s discovery may be useful in keeping crops healthy. In a new study, he tested dispersin B for possible agricultural use. He first coated tobacco leaves with bacteria and incubated the leaves overnight. As he expected, the bacteria completely destroyed the leaves. He then created a genetically modified tobacco plant whose leaves express dispersin B. When the transgenic leaves were coated with bacteria and incubated, they completely resisted infection even after an entire week. While there is no need to modify tobacco, Kaplan says, in theory, genetically modified crops of disease-resistant rice and potatoes might one day be developed.
“Some crops in the U.S. are genetically modified crops, but they’re not popular here,” he says. “But in other parts of the world, genetically modified food is much more acceptable. In Asia, for example, rice blight is a major problem that we may be able to help curb.”
As for the future, Kaplan plans to continue his work with biofilms and other microorganisms. After all, there seems to be no end to the little things he might uncover that could make a huge difference.