|
Researchers at the University of California, Santa Cruz, havedeveloped a novel approach for eradicating drug-resistant bacteriafrom wounds and skin infections, using light to trigger thecontrolled release of nitric oxide. The UCSC team developed aphotoactive compound that releases nitric oxide when exposed tolight, and loaded it into a porous, biocompatible material thatcould be applied as a sprayable powder. In laboratory tests, the light-triggered nitric oxide treatmenteradicated a highly drug-resistant strain of Acinetobacter baumannii, a type of gram-negative bacteria that causes hard-to-treat andpotentially lethal infections throughout the world, includingserious infections in soldiers wounded in Iraq and Afghanistan. Theteam led by Pradip Mascharak, professor of chemistry andbiochemistry at UC Santa Cruz, and graduate student Brandon Heilmanpublished their results in the Journal of the American Chemical Society (JACS). The paper is currently available online and will befeatured on the cover of a future print issue of the journal. Nitric oxide has potent antimicrobial effects and is known to playa role in the immune system and promote wound healing. Gaseousnitric oxide has been used to treat infected wounds, but handlingthe toxic and reactive gas poses many challenges. So researchershave begun exploring a variety of other methods for deliveringnitric oxide as an antibiotic treatment. Because nitric oxide attacks a large number of targetsin microorganisms, including DNA, proteins, and lipids, manyscientists expect bacteria will not easily develop resistance toit. Mascharak's lab developed a photoactive manganese nitrosyl, acompound that rapidly releases nitric oxide when exposed to light.As a carrier for this compound, the researchers used a poroussilicate material known as MCM-41, which traps the photoactivecompound inside its pores. They also tested a relatedaluminosilicate material (Al-MCM-41), which holds the photoactivecompound even more tightly. Tests showed that after thelight-triggered release of nitric oxide, the byproduct of thereaction remains trapped inside the powdery, biocompatiblematerial. "It only delivers nitric oxide. The rest remains trapped in thematerial, which can be washed out of the wound," Mascharak said."We think it could be used as a sprayable powder for treatingbattlefield wounds." Acinetobacter baumannii has earned the nickname "Iraqibacter" because it has caused somany serious infections in soldiers wounded in Iraq. Some strainsof the bacteria are resistant to virtually all antibiotics.Mascharak's lab tested their compound against a strain, isolatedfrom a soldier injured in Afghanistan, that showed resistance tonine of 11 antibiotics tested. To test the photoactive compound, the researchers developed alaboratory model of skin and soft-tissue infections. A standardantibacterial assay involves growing bacteria on the surface of anagar plate (a petri dish with a layer of firm, gelatin-like growthmedium). In an infection, however, bacteria are not only on thesurface but also deeper within the skin or soft tissues. "Werealized that there wasn't a good model for in vitro testing ofantibiotics against soft-tissue infections," Heilman said. To more closely mimic the conditions in an infected wound, Heilmanmixed bacteria into a warm solution of "soft brine agar" and pouredthat onto agar plates to solidify. The bacteria then grewthroughout a 1.1-millimeter-thick layer of soft agar, allowinggrowth and colonization to occur in a manner similar to that seenin skin and soft-tissue infections. Heilman then applied the aluminosilicate powder, with and withoutthe photoactive manganese nitrosyl compound, to a defined area ofthe plates before shining visible light on them. The releasednitric oxide effectively cleared the bacteria from the treatedareas of the plates, showing that the nitric oxide easilypenetrated through the agar layer. The amount of light used toactivate the compound (100 milliWatts per square centimeter) is atypical light flux on a sunny day, Mascharak said. The ability to control the release of nitric oxide using light is asignificant advantage for clinical applications, he added. Testsshowed that illumination of the material causes a steady release ofnitric oxide, which can be stopped and started repeatedly byturning the light off and on. In the field, this could beaccomplished by covering and uncovering the treated area. "This is the first proof-of-concept to show that it works,"Mascharak said. In the paper, the researchers concluded that "It isexpected that application of these nitrosyl-containing porousmaterials to infected wounds followed by exposure to sunlight willbring about a rapid reduction of the pathogen load." The researchers now hope to find collaborators who can help themwith the next levels of testing needed to develop the clinicalpotential of their compound. Additional References Citations. We are high quality suppliers, our products such as Programing Microcontrollers , China STC MCU for oversee buyer. To know more, please visits 8051 Microcontroller Mini Projects.
Related Articles -
Programing Microcontrollers, China STC MCU,
|
