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Blasting Biofilms

Specially tailored viruses could eradicate chronic bacterial infections.

When bacteria team up in sticky communities called biofilms, they can be nearly impossible for conventional antibiotics to eradicate. Biofilms, which often form on hard surfaces such as catheters and water pipes, can cause gingivitis and chronic ear infections. They can also clog up pipes, causing environmental and industrial problems.

MIT researchers are developing viruses to combat biofilms like this one, a group of bacteria growing inside a catheter.

Working with Boston University synthetic biologist James Collins, ­Harvard-MIT graduate student Timothy Lu has designed a new, highly effective means of dispersing and killing the bacteria living in biofilms. The two researchers have engineered viruses that attack both the bacteria and the carbohydrates that hold them together–eliminating, for example, more than 99 percent of the E. coli in a model biofilm. If such bacteria-attacking viruses prove safe for industrial and clinical use, researchers could develop stocks of different kinds of viruses, each tailored to attack a different kind of biofilm.

Because they are protected by a sticky carbohydrate scaffold called a matrix, bacteria living communally in biofilms are a thousand times as resistant to antibiotics as free-­swimming bacteria are, says Collins. The matrix blocks antibiotics and human immune-system cells; it even provides something like a primitive circulatory system, distributing nutrients to cells throughout the biofilm.

Large doses of antibiotics can usually eradicate these infections, but there is some worry that drug-­resistant biofilm infections are becoming more common. New treatments are needed for recurrent infections, such as chronic ear infections in children, that antibiotics knock down only temporarily. What’s more, some evidence suggests that the use of antibiotics actually induces biofilm formation.

Collins and Lu select a naturally occurring virus that already attacks a troublesome bacterium, such as E. coli or Staphylococcus. They then insert a new gene into the virus, one that codes for an enzyme that dissolves the main carbohydrate component of the biofilm matrix. (Naturally occurring viruses can attack biofilms, but the researchers’ genetic modifications increased viruses’ effectiveness by two orders of magnitude.) The viruses they work with, called bacteriophages, specialize in infecting bacteria. They replicate inside bacterial cells; burst them open, killing the bacteria; and then spread to other bacterial cells. But bacteriophages do not harm animal cells or bacteria other than their targets.

The new technique will allow researchers to build bacteriophage cocktails for attacking all kinds of biofilms. Because industrial standards are easier to meet than U.S. Food and Drug Administration requirements, the first such cocktails are likely to show up in industry rather than in the clinic.

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