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Zapping microbes with lasers and enzymes

New tools could help fight the growing ranks of antibiotic-resistant bacteria

Image: Methicillin-resistant Staphylococcus aureus bacteria
Fighting drug-resistant bacteria
Researchers are aiming lasers and a common enzyme found in tears at disease-causing bacteria, such as the MRSA strain pictured above. Such strategies may help stem the growing tide of multidrug-resistant microbes and prevent the spread of infections, respectively.
Jeff Hageman / CDC
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Image: Bryn Nelson
Bryn Nelson

Researchers fighting the rise of drug-resistant bacteria have found a new guiding light and tapped into the cleansing power of a good cry.

Among several promising new ways in which technology is aiding the crisis over drug resistance, British researchers have developed a laser-activated dye system that wipes out microbes. Separately, an antibacterial enzyme found in human tears, lysozyme, is receiving a 21st century makeover from Alabama scientists in a scheme to use ultra-strong carbon nanotubes to lock lysozyme into place for coating susceptible surfaces.

The laser-activated dye could become a potent new weapon in the arsenal aimed at fighting the growing ranks of antibiotic-resistant bacteria, said Michael Wilson, a professor of microbiology at University College London's Eastman Dental Institute.

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The worst example is methicillin-resistant Staphylococcus aureus (abbreviated MRSA), which is responsible for many life-threatening infections. Ominously, some strains of MRSA are becoming resistant to the powerful antibiotic vancomycin — considered by many researchers as one of the last lines of defense. In 2005, about 94,360 people in the United States acquired serious MRSA infections, mostly in hospitals and other healthcare settings. Of those, about one in five subsequently died, according to the Centers for Disease Control and Prevention.

Community-acquired MRSA infections, although generally less severe, also are on the rise. Among recent high-profile cases, high school football players, wrestlers and other athletes have acquired MRSA infections through skin-to-skin contact.

Zapping microbes
The new laser approach published by Wilson and colleagues earlier this month in the journal BMC Microbiology could help in two ways. First, it could be used to treat infections from resistant organisms that can no longer be killed by conventional drugs. Second, he said, if deployed instead of antibiotics to treat wound infections, those antibiotics could be used less frequently, which would reduce the opportunities for bacteria to develop resistance to them.

The near-infrared light emitted by the laser is absorbed by indocyanine green, converting the dye to a high-energy form that donates its newfound energy to oxygen, water and other nearby molecules. The result is the formation of highly reactive molecules known as singlet oxygen, hydroxyl radicals and free radicals that attack the cell wall and innards of bacteria. Once indocyanine green has passed along its energy, it reverts back to its normal state, allowing it to absorb more laser light and repeat the process.

Because of its nonspecific way of killing bacteria, Wilson said, the system is effective against many different pathogenic species, including Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa. The laser, he said, also benefits from its potential ability to treat any localized infections that are accessible to laser light and dye application, such as burns, abscesses, bed sores, ulcers and other exterior wounds. While the system also does its job without raising the temperature, Wilson noted, it cannot be used for systemic infections that would require internal access.

Researchers at Rockefeller University in New York may have found a new drug to kill that gap with Ceftobiprole, which targets the actual gene conferring drug resistance in MRSA and other bacteria and has been shown to kill those Staphylococcus strains that have developed resistance to vancomycin. But ultimately, a nonspecific approach that attacks on many fronts may be harder for pathogens to overcome.

“We can never be confident that this approach will not lead to resistance,” Wilson said of the laser technique. Nevertheless, he said, the creation of free radicals by the interaction of the laser and the dye disrupts many metabolic processes and structures instead of targeting a specific molecule, process, or structure that could escape destruction through a genetic mutation. “This means that, in order to become resistant, a whole range of simultaneous beneficial mutations would have to occur — this is extremely unlikely,” he said.

Wilson’s team is currently trying to determine the best concentration of laser light and indocyanine green for the system to be effective in human patients. The dye, sold under the brand name IC-GREEN, is already approved by the Food and Drug Administration as a medical diagnostic, particularly for testing heart, liver and eye function. Wilson said his group is also planning a clinical study to gauge the effectiveness of the laser approach for treating infections in burn patients.

“I think it’s a great idea,” said Frank DeLeo, acting chief of the Laboratory of Human Bacterial Pathogenesis at the National Institute of Allergy and Infectious Diseases’ Rocky Mountain Laboratories in Hamilton, Mont. DeLeo noted that other researchers have taken a similar approach with the photo-activated and FDA-approved dye methylene blue, which targets bacterial DNA. An increasing body of literature, he said, suggests that this general strategy could work well not only for MRSA but also for other worrisome bacteria.

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