In one of the first potential applications of synthetic biology, an emerging field that aims to design and build useful biomolecular systems, researchers from MIT and Boston University are engineering viruses to attack and destroy the surface biofilms that harbor harmful bacteria in the body and on industrial and medical devices.
They have already successfully demonstrated one such virus, and thanks to a plug and play library of parts believe that many more could be custom-designed to target different species or strains of bacteria.
The work, reported in the July 3 Proceedings of the National Academy of Sciences, helps vault synthetic biology from an abstract science to one that has proven practical applications. "Our results show we can do simple things with synthetic biology that have potentially useful results," says first author Timothy Lu, a doctoral student in the Harvard-MIT Division of Health Sciences and Technology.
Bacterial biofilms can form almost anywhere, even on your teeth if you don't brush for a day or two. When they accumulate in hard to reach places such as the insides of food processing machines or medical catheters, however, they become persistent sources of infection.
These bacteria excrete a variety of proteins, polysaccharides, and nucleic acids that together with other accumulating materials form an extracellular matrix, or in Lu's words, a slimy layer," that encases the bacteria. Traditional remedies such as antibiotics are not as effective on these bacterial biofilms as they are on free-floating bacteria. In some cases, antibiotics even encourage bacterial biofilms to form.
Lu and senior author James Collins, professor of biomedical engineering at BU, aim to eradicate these biofilms using bacteriophage, tiny viruses that attack bacteria. Phage have long been used in Eastern Europe and Russia to treat infection.
For a phage to be effective against a biofilm, it must both attack the strain of bacteria in the film and degrade the film itself. Recently, a different group of researchers discovered several phages in sewage that meet both criteria because, among other things, they carry enzymes capable of degrading a biofilm's extracellular matrix.
This discovery led Lu and Collins to consider engineering phages to carry enzymes with similar capabilities. Why" Finding a good naturally occurring combination for a given industrial or medical problem is difficult. Plus, "`people don't want to dig through sewage to find these phages," says Lu.
So Collins and Lu defined a modular system that allows engineers to design phages to target specific biofilms. As a proof of concept, they used their strategy to engineer T7, an Escherichia coli-specific phage, to express dispersin B (DspB), an enzyme known to disperse a variety of biofilms.
To test the engineered T7 phage, the team cultivated E. coli biofilms on plastic pegs. They found that their engineered phage eliminated 99.997% of the bacterial biofilm cells, an improvement by two orders of magnitude over the phage's nonengineered cousin.