This Behind the Scenes article was provided to LiveScience in partnership with the National Science Foundation.
A new compound that releases nitric oxide when exposed to light offers a treatment to help those infected by the potentially lethal bacteria Acinetobacter baumannii.
Resistant to most antibiotics, A. baumannii enters the body through open wounds and generally strikes against people with compromised immune systems. Symptoms of A. baumannii may include fever, swollen or painful areas or wounds, blistering, trouble breathing, and headaches. The bacterium has become especially prevalent in soldiers wounded in Iraq, inspiring the nickname "Iraqibacter".
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A team led by UC Santa Cruz chemistry professor Pradip Mascharak and his graduate student Brandon Heilman developed a compound that, in lab tests, eradicated a highly resistant strain of A. baumannii. The compound consists of photoactive manganese nitrosyl — which releases nitric oxide when it is exposed to light — contained in either a powdery silicate material (MCM-41) or an aluminosilicate material (Al-MCM-41). The powder, designed to be sprayed directly into the wound, releases nitric oxide and kills the A. baumannii when exposed to light — even just broad daylight.
Mascharak explained that this method is especially novel because the byproduct of the nitric oxide reaction does not enter the wound — it is retained in the powder itself, allowing only nitric oxide to enter the body, preventing side effects.
"We believe [this] is a major breakthrough," said Mascharak. "Although the antibiotic action of nitric oxide on pathogens was known for sometime, the convenient delivery of this toxic gas to wounds has been a problem."
The teams' research, which was supported by the National Science Foundation, was featured in an article and on the cover of the July 18 issue of the Journal of the American Chemical Society.
To test this compound, Mascharak and his team grew the A. baumannii in agar films, which allowed the bacteria to grow and colonize as it might in skin and soft-tissue infections. The strain used for this test was isolated from a soldier wounded in Afghanistan and was previously resistant to nine of 11 antibiotics tested as treatments.
Then the team added the powder — with and without the compound — to the agar plates. The researchers exposed the plates to 100 milliwatts per square centimeter of light (approximately the amount of light on a sunny day), and within 24 hours the bacteria treated with the compound were completely cleared. When the team tried to grow this same bacteria culture after it was exposed to the compound, it would not grow, proving that the A. baumannii was successfully eradicated.
Not only is this compound proven to be effective in lab tests, it's user-friendly. The powder is simple to dispense, and the small amount required for effectiveness — just a very thin layer — means a little powder can treat many victims. The powder also can be easily transported and stored in most conditions, as long as it is sheltered from light.
This form of the nitric oxide delivery offers inspiration for other medical applications using nitric oxide.
"We have previously shown that light-triggered nitric oxide delivery can wipe out other bacteria, like staph [Staphylococcus] quite readily," said Mascharak.
There are other advantages to using nitric oxide for medical treatments:
- It will not accumulate in the body
- It is well-tolerated by host cells
- It has been shown to enhance immune system response
Future plans for Mascharak’s team include testing their treatment against A. baumannii in animal models.
"The next step is to take the work to animal models, where real wounds infected with the bacteria will be treated and the effects of the nitric oxide exposure will be evaluated," said Mascharak. "We are trying to set up collaborative efforts along this direction with people who are experts with such evaluation procedures."
Editor's Note: The researchers depicted in Behind the Scenes articles have been supported by the National Science Foundation with funding basic research and education across all fields of science and engineering. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author and do not necessarily reflect the views of the National Science Foundation. See the Behind the Scenes Archive.
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