Researcher’s Work On Bacteria,
Unseen and potentially dangerous newcomers move into town, build condominiums, and begin to organize. They talk to each other constantly, creating an intricate network of connections and signaling passersby to join them. Soon the condo complex threatens to take over the town. That’s when bio-engineer Thomas Wood gets involved. The process is an analogy he uses to explain his work with bacteria and biofilms. Wood, recently named the Northeast Utilities Chair in Environmental Engineering Education, is finding ways to break up the “talking” that enables bacteria to congregate and create biofilms. The elaborate structures that bacteria build look like condominiums, Wood explains, displaying a slide that supports his analogy. They have odd shapes and a series of water channels between them where water brings in nutrients and removes wastes. The bacteria in biofilms secrete chemical signals that enable them to “talk” to each other and form films by turning genes off and on. The bacteria can detect which cells are nearby and what their density is. What biologists call biofilms, laymen might call slime. The slippery rock in the river and a person’s unbrushed teeth are covered with biofilms. Many biofilms are far from benign. They are often responsible for chronic, antibiotic-resistant infections. They can corrode ships’ hulls. They can grow on fishing nets, causing fishermen to suffer commercial losses. The fishing net problem led to one of Wood’s most recent biofilm research projects, in which he examined the chemical and genetic properties in a natural compound that could stop the bacteria from “talking.” When bacteria are unable to send out signals to other bacteria, biofilm formation is held in check. This non-toxic, naturally occurring compound, one of a group of chemicals known as furanones, is found in a seaweed off the coast of Australia. The furanone, which developed over billions of years, doesn’t necessarily kill bacteria, but it stops them from forming biofilms that would kill the seaweed. The furanone was discovered by Australians in a quest to find a solution to a commercial problem – how to keep fishermen’s nets from becoming slimy. When they published an article about this “miracle” material, Wood became interested in its chemical and genetic properties. He now makes furanone synthetically in his lab. His fundamental discoveries about the compound, published in scholarly articles, have attracted the collaboration of researchers at New York University Medical School who are developing a new vaccine that could be used as an antidote to anthrax. The NYU researchers were interested in Wood’s discovery that furanone prevents Bacillus subtilis, a common rod-shaped bacteria, from sending the signals that are needed for biofilm formation. Furanone kills bacteria that are classified as Gram-positive and it prevents those that are Gram-negative from “talking.” In the case of B. subtilis, a Gram-positive bacteria, it does both – preventing its toxin genes from being turned on and killing it. To determine how compounds such as furanone work, Wood and his research group are sifting through the 4,000 genes in a bacterium, to see which ones the compound affects. They use E. coli, a common and well-studied bacterium, as a reference point, comparing how the compound affects its genes and those of other bacteria. Wood’s original funding for fundamental research on biofilms came from the Electric Power Research Institute, which was interested in controlling biofilm formation in nuclear reactors and in preventing the growth of corrosion-causing bacteria. One of his current funding sources is a small drug discovery company in San Diego, Sequoia Sciences, which separates plants into their component chemicals and provides compounds from natural sources for biological screening. Half of the dozen graduate students working with Wood are now screening 15,000 plants from all over the world, looking for other compounds that might, like furanone, stop the formation of biofilms. A promising discovery they’ve made is ursolic acid, which comes from Diospyros dendo, a tree from Gabon, Africa, that is a source of ebony for black piano keys. They’ve shown that it can inhibit biofilm formation by E. coli without affecting the bacteria’s growth rate. It appears that ursolic acid affects motility, making the bacteria move away rather than staying still and building communities, Wood says. Wood supplies synthetic furanone to NYU medical researchers who are trying its effects on Bacillus anthracis, a bacterium that is closely related to B. subtilis and that causes anthrax. The NYU researchers, headed by Dr. Martin Blaser, chairman of the Department of Medicine, are in the initial stages of testing a potential new anthrax vaccine and, with Wood, have applied for a patent on it. “We’re definitely just at the beginning of this process,” Wood says. He does not conduct any of the B. anthracis testing at UConn. Wood already has a patent for using a living, biofilm “paint” to inhibit corrosion, and has applied for one on making chemicals in a process that uses engineered enzymes. Wood joined the UConn faculty in 1998, coming from the University of California, Irvine, where he began his academic career after receiving his Ph.D. from North Carolina State University in 1991. His range of research interests is reflected in his dual appointment at UConn in the Departments of Chemical Engineering and Molecular and Cell Biology. |