Operate a chemical response of the body's immune system to attack pathogens by using copper

Operate a chemical response of the body's immune system to attack pathogens by using copper -

exploit a natural process in the body that pumps lethal doses of copper fungi and bacteria shows promise as a new way to kill infectious microbes, a report team of scientists from Duke University.

Publishing in July 31, 2014, issue of Chemistry & Biology , the researchers describe a mode of operation the unique chemical response of the body's immune system to attack the agents pathogens using copper, long known for its antimicrobial properties, in a manner that minimizes damage to the body.

results in cell and animal models represent progress in developing broad-spectrum antimicrobial agents on the basis of the copper biology -. advance a much needed face escalating antibiotic resistance and threatening fungal infections

"There is a clear need for new strategies for antimicrobial therapies," said lead author Dennis J . Thiele, Ph.D., George Barth Geller Professorof Pharmacology and cancer Biology and biochemistry at Duke University medical school. "copper, while essential, can be toxic when mismanaged by the body, but our work shows that we can activate the antimicrobial potential of the targeted metal that focuses on immune cells and prevents a copper imbalance in the body. "

Thiele, who studied copper biology for over 30 years, teamed up with Katherine J. Franz, Ph.D., Alexandre F. Hehmeyer associate professor of chemistry at Duke University, use a small molecule created earlier in the Franz laboratory that primarily supports additional copper to specialized chambers within immune cells called macrophages.

Faced with fungal or bacterial infections, macrophages ingest and try to destroy pathogens by enclosing them in tiny rooms of death and triggering an oxidative burst of hydrogen peroxide, the oxide nitric and other poisons, including copper. But both fungi and bacteria deploy chemical attack resistance mechanisms in macrophages compartments.

Thiele, Franz and his colleagues used a clever chemical trick that takes advantage of this offensive oxidation selectively to release the active molecule macrophage death chambers. The molecule then synergizes with copper already present in the cells to kill microbial pathogens. The strategy is designed to protect healthy cells avoiding binding in cells that are not infected by copper.

"This provides a strategy for the development of compounds that exploit the immune response activated and replace fungal copper detoxification machinery and pathogenic bacteria to stimulate own antimicrobial activity of the body," said Franz.

Thiele said that future studies will focus on improving the properties of drugs as the molecule to maximize its ability to fight against additional fungal and bacterial infections in animal models. They also continue to explore how the molecule works and whether the related molecules can deliver payloads additional metal, including silver, which also has antimicrobial properties.