Bioengineered viruses kill bacteria
Synthetic biology is an emerging field which involves the engineering of biological organisms. One of the first applications has been developed by a team of researchers from the MIT and Boston University who built viruses to combat harmful 'biofilms'. These bacteriophages -- or phages -- could soon be used to destroy bacterial biofilms in hard to reach places such as the insides of food processing machines. These phages are not allowed for use in humans in the U.S., but they could be approved for future phage-containing drugs for use in livestock.
The above figure shows how an engineered virus, T7, uses a two-pronged attack strategy to destroy a biofilm composed of E. coli bacteria (Credit: Timothy Lu and James Collins). This research has been led by James Collins, professor of biomedical engineering at Boston University, at his Applied BioDynamics Laboratory. He's working with Timothy Kuan-Ta Lu on "novel methods of eliminating bacterial biofilms." In this lab, they are "modeling and building synthetic gene networks for a variety of biotechnology and biocomputing applications. [They] are also using engineered gene networks to study general principles underlying gene regulation.]
Before going further, what exactly are biofilms? Here are the researchers' answer. "Biofilms have only recently become recognized as a dominant form of bacterial life. Biofilms are multi-cellular communities made up of bacteria, polysaccharides, nucleic acids, and various other components. Bacteria living in the biofilm state are more resistent to antibiotics and can cause chronic infections in humans in addition to causing substantial damage to man-made devices such as pipes and water towers."
So what exactly Lu and Collins have done? [They] "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.
This looks remarkably efficient, but limited to one kind of bacteria. Not so fast, say the researchers, who think their approach can be used with many other bacteria. "The team's modular strategy can be thought of as a 'plug and play' library, says Collins. "The library could contain different phages that target different species or strains of bacteria, each constructed using related design principles to express different enzymes." Creating such a library may soon be feasible with new technologies for synthesizing genes quickly and cheaply."
This research work has been published in the Proceedings of the National Academy of Sciences under the name "Dispersing biofilms with engineered enzymatic bacteriophage" (Vol. 104, No. 27, Pp. 11197-11202, July 3, 2007). Here is a link to the abstract which starts like this. "Synthetic biology involves the engineering of biological organisms by using modular and generalizable designs with the ultimate goal of developing useful solutions to real-world problems. One such problem involves bacterial biofilms, which are crucial in the pathogenesis of many clinically important infections and are difficult to eradicate because they exhibit resistance to antimicrobial treatments and removal by host immune systems. To address this issue, we engineered bacteriophage to express a biofilm-degrading enzyme during infection to simultaneously attack the bacterial cells in the biofilm and the biofilm matrix, which is composed of extracellular polymeric substances."
This paper has been published as an "open access article." So here are two links to the whole article, in HTML format and in in PDF format (6 pages, 1.66 MB). The above illustration has been extracted from this article.
Sources: Elizabeth Dougherty, Harvard-MIT Division of Health Sciences and Technology July 6, 2007; and various websites
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