[Editors] MIT, BU team builds viruses to combat harmful 'biofilms'

[Elizabeth Thomson]

MIT News Office
Massachusetts Institute of Technology
Room 11-400
77 Massachusetts Avenue
Cambridge, MA  02139-4307
Phone: 617-253-2700
http://web.mit.edu/newsoffice/www

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MIT, BU team builds viruses to combat harmful 'biofilms'

--Work is step forward for synthetic biology
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For Immediate Release
MONDAY, JULY 9, 2007
Contact: Elizabeth A. Thomson, MIT News Office
Phone: 617-258-5402
Email: thomson at mit.edu

OR

Kira Edler Jastive, Boston University Office of Media Relations
Phone: 617-358-1240
E-mail: kedler at bu.edu

DIAGRAM AVAILABLE


CAMBRIDGE, Mass.--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.

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. “We hope in a few years,  
it will be easy to create libraries of phage that we know have a good  
chance of working a priori because we know so much about their inner- 
workings,” says Lu.

Synthetic biology also makes it possible to control the timing of  
when a gene is expressed in an organism. For instance, Lu inserted  
the DspB genes into a precise location in the T7 genome so that the  
phage would strongly express it during infection rather than before  
or after. Such control was possible because T7 was extremely well  
characterized by other researchers such as MIT synthetic biologist  
Drew Endy, an assistant professor of biological engineering.

Though phages are not approved for use in humans in the United  
States, recently the FDA approved a phage cocktail to treat Listeria  
monocytogenes on lunchmeat. This  makes certain applications, such as  
cleaning products that include phages to clear slime in food  
processing plants, more immediately promising. Another potential  
application: phage-containing drugs for use in livestock in exchange  
for or in combination with antibiotics.

This work is supported by the Department of Energy and the National  
Science Foundation. Lu was supported by a Howard Hughes Medical  
Institute predoctoral fellowship and an HST Medical Engineering/ 
Medical Physics fellowship.

--MIT--

Written by Elizabeth Dougherty, Harvard-MIT Division of Health  
Sciences and Technology