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Biomedicine

Using Viruses to Kill Bacteria

In the fight against infection, viruses may take up where antibiotics leave off.

Hospitals are fertile ground for infectious bacteria, which can spread rapidly across countertops, stethoscopes, and catheters. These “superbugs” infect up to 1.2 million patients a year in the United States, according to a 2007 report from the Association for Professionals in Infection Control and Epidemiology, and they’re quick to evolve defenses against even the most powerful antibiotics.

In stitches: Hospital sutures coated with a bacteria-fighting virus (shown above) effectively killed off 96 percent of an antibiotic-resistant bacteria in culture. Researchers used these same sutures to sew up bacterially infected wounds in live rats. The treated stitches prevented infection from flaring up, while rats with untreated sutures developed large sores and inflammation.

Now scientists in Scotland have come up with an alternative to antibiotics, which may effectively stop bacteria in its tracks. Janice Spencer and a team of researchers at the University of Strathclyde are developing nylon sutures coated with bacteriophages–viruses, found naturally in water, that eat bacteria while leaving human cells intact. New research by the Scottish team found that phage-coated sutures effectively stemmed infection in live rats.

Bacteriophages are not a recent discovery. During World War II, Russian doctors used cocktails of these viruses to treat soldiers infected with bacteria such as dysentery and gangrene. However, researchers soon turned their attention from bacteriophages to the rapidly rising field of antibiotics, developing new classes of antibiotics to combat ever-more-resistant strains of bacteria.

“Now we’re coming to the end of the usefulness of antibiotics,” says Spencer. “It takes time to get new classes of antibiotics onto the market, whereas bacteriophages can be easily isolated from environmental sources such as sewage water.”

In water, these natural-born killers are extremely effective at eating up bacteria. The virus binds to bacteria and injects its DNA, replicating within its host until it reaches capacity, whereupon it bursts out, killing the bacteria in the process.

Obtaining bacteriophage-laden water samples is easy, says Spencer. The challenge is in keeping virus molecules active out of water. In dry environments, the virus’s proteins tend to fall apart in a matter of hours, rendering them ineffective against bacteria. Spencer and her colleagues isolated bacteriophages from water samples and developed a novel method to keep them active.

The team chemically bound bacteriophages to microscopic polymer beads by first breaking the surface of the polymer. Then the researchers added a linker molecule to the polymer’s surface, which in turn binds to bacteriophages and keeps them from falling apart. To test the virus’s virulence, the team first made small incisions in live rats, then infected them with Methicillin-Resistant Staphylococcus Aureus (MRSA), one of the most resistant strains of bacteria found in hospitals. Half of the rats were stitched up with sutures that were coated with polymer-bound bacteriophages. The other rats were closed up with untreated sutures.

Spencer and her colleagues found that the wounds dressed with the treated sutures appeared to have no infection, while those stitched with regular sutures became inflamed, with large sores and “abundant pus.”

The researchers further tested the bacteriophages’ effectiveness, removing the treated sutures and placing them directly into a culture dish full of MRSA bacteria, obtained from patients in three different U.K. hospitals. They found that the virus remained active for up to three weeks, effectively killing off 96 percent of bacteria in culture.

Spencer says that, while bacteriophages will not completely replace antibiotics in fighting infection, these viruses have important advantages. “Antibiotics are broad-spectrum, and for certain bacterial strains, it’s easier to use bacteriophages if you know exactly which bacterium is causing the infection,” she says. “[With bacteriophages,] you can target one strain, and it wouldn’t affect any other bacteria that may be protecting cells.”

Synthetic biologist James Collins recently engineered viruses that kill off colonies of bacteria, called biofilms. Collins, a professor of biomedical engineering at Boston University, says that Spencer’s technique clears many hurdles that have stymied bacteriophage use in the past. “It can be a surface-mounted bacteriophage, so instead of worrying about issues of ingesting a virus, by limiting application to the surface, they get around that concern,” he says. “I suspect there might be interest in the Defense Department to use this early to treat infections in soldiers on the battlefield.”

The Scottish team also hopes to incorporate microscopic beads of bacteriophages into sprays and creams, which, once dry, can remain active against bacterial infection for prolonged periods of time. The researchers are also exploring other methods of binding bacteriophages onto polymers, including a process known as corona discharge, which is commonly used to imprint ink onto plastic supermarket bags. The method involves a burst of high-voltage electricity, which acts to break up a polymer surface. Spencer says that this technique, patented by the University of Strathclyde, may improve the binding between polymer beads and bacteriophages.

In addition to therapeutic applications, bacteriophages may be useful in detecting bacterial infection, and the Scottish team has plans to investigate bacteriophages’ diagnostic potential.

Spencer presented the group’s findings at a recent meeting of the Society for General Microbiology, and since then, she has received queries from hospitals and pharmaceutical companies that have expressed interest in an antibiotic alternative. Currently, the team is in negotiations with Gangagen, a Canada-based biotechnology company that works on bacteriophage-based therapies.

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