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Light-Triggered Anti-Bacterial Technology Developed

Acinetobacter bacillus (CDC.gov)

Acinetobacter bacillus (CDC.gov)

Researchers at University of California-Santa Cruz have developed a method for eradicating drug-resistant bacteria from wounds and skin infections, using light to trigger the release of the chemical nitric oxide. The team led by biochemistry professor Pradip Mascharak published its findings online in the Journal of the American Chemical Society (paid subscription required).

The UC Santa Cruz researchers targeted a drug resistant strain of Acinetobacter baumannii, a bacteria that causes hard-to-treat and potentially lethal infections. The bacteria has been associated with antibiotic-resistant infections among wounded soldiers in Iraq and Afghanistan.

Nitric oxide has well-documented anti-microbial effects and is known to encourage wound healing. Because nitric oxide attacks a large number of targets in microorganisms, including DNA, proteins, and lipids, the bacteria is not expected to easily develop resistance to the chemical.

Gaseous nitric oxide has been used to treat infected wounds, but handling the toxic and reactive gas poses many challenges. Thus the researchers sought an alternative, safer method for its delivery.

Mascharak’s lab developed a photoactive form of 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 that traps the photoactive compound inside its pores.

The UC Santa Cruz team also tested a variety of MCM-41 treated with aluminum (Al-MCM-41) that 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.

The researchers tested the compound against a strain of Acinetobacter baumannii isolated from a soldier injured in Afghanistan, which showed resistance to nine of 11 antibiotics tested. To test the photoactive compound, however, the researchers needed to develop a more realistic lab model of skin and soft-tissue infections.

The standard antibacterial assay normally involves growing bacteria on the surface of an agar plate, a petri dish with a layer of firm, gelatin-like growth medium. Graduate student and first author Brandon Heilman instead mixed bacteria into a warm solution of soft brine agar and poured that onto agar plates to solidify.

This test environment more closely resembles infections, where bacteria are not only on the surface but also deeper within the skin or soft tissues. The bacteria then grew throughout a 1.1-millimeter-thick layer of soft agar, allowing growth and colonization to occur in a manner similar to that seen in skin and soft-tissue infections.

Heilman then applied the aluminosilicate powder, with and without the photoactive manganese nitrosyl compound, to a defined area of the plates before shining visible light on them. The amount of light used to activate the compound — 100 milliwatts per square centimeter — say the authors, is a typical light flux on a sunny day.

The released nitric oxide effectively cleared the bacteria from the treated areas of the plates, showing that the nitric oxide penetrated through the agar layer. The tests indicate that illumination of the material results in a steady release of nitric oxide, which can be stopped and started repeatedly by turning the light off and on. In the field, this could be accomplished by covering and uncovering the treated area.

“This is the first proof-of-concept to show that it works,” says Mascharak. The researchers hope to find collaborators who can help them with the next levels of testing needed to develop the clinical potential of their compound. “We think it could be used as a sprayable powder for treating battlefield wounds,” Mascharak adds.

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