New photoactive compound eradicates 'Iraqibacter' from wounds and skin infections

Published on May 31, 2012 at 5:41 AM · No Comments

Researchers at the University of California, Santa Cruz, have developed a novel approach for eradicating drug-resistant bacteria from wounds and skin infections, using light to trigger the controlled release of nitric oxide. The UCSC team developed a photoactive compound that releases nitric oxide when exposed to light, and loaded it into a porous, biocompatible material that could be applied as a sprayable powder.

In laboratory tests, the light-triggered nitric oxide treatment eradicated a highly drug-resistant strain of Acinetobacter baumannii, a type of gram-negative bacteria that causes hard-to-treat and potentially lethal infections throughout the world, including serious infections in soldiers wounded in Iraq and Afghanistan. The team led by Pradip Mascharak, professor of chemistry and biochemistry at UC Santa Cruz, and graduate student Brandon Heilman published their results in the Journal of the American Chemical Society (JACS). The paper is currently available online and will be featured on the cover of a future print issue of the journal.

Nitric oxide has potent antimicrobial effects and is known to play a role in the immune system and promote wound healing. Gaseous nitric oxide has been used to treat infected wounds, but handling the toxic and reactive gas poses many challenges. So researchers have begun exploring a variety of other methods for delivering nitric oxide as an antibiotic treatment. Because nitric oxide attacks a large number of targets in microorganisms, including DNA, proteins, and lipids, many scientists expect bacteria will not easily develop resistance to it.

Mascharak's lab developed a photoactive manganese nitrosyl, a compound that rapidly releases nitric oxide when exposed to light. As a carrier for this compound, the researchers used a porous silicate material known as MCM-41, which traps the photoactive compound inside its pores. They also tested a related aluminosilicate material (Al-MCM-41), which holds the photoactive compound even more tightly. Tests showed that after the light-triggered release of nitric oxide, the byproduct of the reaction remains trapped inside the powdery, biocompatible material.

"It only delivers nitric oxide. The rest remains trapped in the material, which can be washed out of the wound," Mascharak said. "We think it could be used as a sprayable powder for treating battlefield wounds."

Acinetobacter baumannii has earned the nickname "Iraqibacter" because it has caused so many serious infections in soldiers wounded in Iraq. Some strains of the bacteria are resistant to virtually all antibiotics. Mascharak's lab tested their compound against a strain, isolated from a soldier injured in Afghanistan, that showed resistance to nine of 11 antibiotics tested.

To test the photoactive compound, the researchers developed a laboratory model of skin and soft-tissue infections. A standard antibacterial assay involves growing bacteria on the surface of an agar plate (a petri dish with a layer of firm, gelatin-like growth medium). In an infection, however, bacteria are not only on the surface but also deeper within the skin or soft tissues. "We realized that there wasn't a good model for in vitro testing of antibiotics against soft-tissue infections," Heilman said.

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