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Researchers developing phage weapons against biofilms

By Ahmed ElAmin , 11-Jul-2007

Bacteriophage viruses can be engineered to attack and destroy biofilms -- hard to remove pathogens stuck on machinery and other surfaces in manufacturing plants -- according to new research.

 

Biofilms are a major problem at food manufacturing sites. These colonies of pathogens form a tough surface skin that resist conventional commercial washing and sanitizing methods.

 

 

 

Researchers from Massachusetts Institute of Technology (MIT) and Boston University say they are engineering viruses to destroy the surface "biofilms" that harbor harmful bacteria in the body and on industrial and medical devices.

 

 

 

The researchers are labelling their results as one of the first potential applications of synthetic biology, an emerging field that aims to design and build useful biomolecular systems.

 

 

 

They have already successfully demonstrated one such virus, and thanks to a "plug and play" library of "parts", they believe that many more could be custom-designed to target different species or strains of bacteria.

 

 

 

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, and become persistent sources of contamination.

 

 

 

The bacteria excrete a variety of proteins, polysaccharides, and nucleic acids that together with other accumulating materials form an extracellular matrix, or as the researchers say, a "slimy layer" that encases the bacteria.

 

 

 

Researchers Timothy Lu and James Collins aim to eradicate these biofilms using bacteriophage, tiny viruses that attack pathogens.

 

 

 

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, they said.

 

 

 

The discovery led Lu and Collins to consider engineering phages to carry enzymes with similar capabilities.

 

 

 

"Finding a good naturally occurring combination for a given industrial or medical problem is difficult," said Lu.

 

 

 

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, 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 per cent 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, said 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," he stated.

 

 

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," said Lu.

 

 

 

Though phages are not approved for use in humans in the US, the FDA recently 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," they stated.

 

 

 

The work was reported in the 3 July proceedings of the National Academy of Sciences.