MIT team builds viruses to combat harmful biofilms

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.

Bacterial biofilms can form almost anywhere, and when they accumulate in hard-to-reach places such as the insides of food processing machines or medical catheters 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 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.

First author Timothy Lu, a doctoral student in the Harvard-MIT Division of Health Sciences and Technology, and senior author James Collins, professor of biomedical engineering at BU, aim to eradicate these biofilms using bacteriophages, tiny viruses that attack bacteria. Phages 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. 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.

The team's modular strategy can be thought of as a "plug and play" library, explains 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."

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.

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