Biologists Modify Virus to Help Fight Bacteria

A pair of biologists has pioneered an innovative way to fight certain bacterial infections by designing a virus to attack the bacteria. The research has been published online by the Proceedings of the National Academy of Science.

Viruses which prey on bacteria, known as bacteriophages, are frequently modified and used in biotechnological applications. Naturally occurring bacteriophages have been used to treat bacterial infections in the past; more recently, the FDA approved the use of a bacteriophage which attacks the foodborne pathogen Listeria monocytogenes as a food additive. In their new paper, researchers Timothy Lu of Harvard and James Collins describe how they engineered a bacteriophage to be effective against specific bacteria in biofilms.

Biofilms consist of surface-dwelling communities of bacteria which secrete a protective matrix of proteins, sugars, and other substances around themselves. The protection granted by this matrix makes the bacteria in the biofilm extremely resistant to destruction. Biofilms are common in nature, but are of medical interest because they occur as dental plaques and in bacterial infections. They can also occur on man-made surfaces, and due to their persistence through harsh treatment, can be a source of reinfection in medical or industrial settings. Despite their resilience, previous studies have shown that some naturally occuring bacteriophages can degrade the matrix in biofilms to expose the bacteria inside, and researchers have isolated and identified the molecules which grant the matrix-degrading ability.

Lu and Collins state that while it is extremely unlikely that one would be able to find a bacteriophage that was both specific to a strain of bacteria and capable of breaking down the biofilm matrix produced by those bacteria, biotechnology makes it possible for scientists to pick a bacteriophage specific to the bacterium they want to target, and then give that virus the ability to degrade biofilms.

As a proof-of-concept for their idea, the researchers modified the E. coli-specific bacteriophage T7 to induce production of the DspB enzyme, which destroys biofilm matrix components. They then tested the effectiveness of their engineered bacteriophage bacteriophage on E. coli biofilms; the modified T7 was found to be roughly one hundred times more effective at killing the bacteria than the natural T7.

While the authors of the paper are careful to point out that much more research needs to be done before engineered bacteriophages can be used to treat bacterial infections, they also suggest that antibiofilm strategies provide opportunities for better treatment of bacterial infections that may help circumvent the growing problem of antibiotic resistance in bacterial pathogens.

References:

Timothy Lu and James Collins, Dispersing biofilms with engineered enzymatic bacteriophage. Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0704624104; abstract available at http://www.pnas.org/cgi/content/abstract/0704624104v1, PDF of full article available at http://www.pnas.org/cgi/reprint/0704624104v1