Harnessing a natural process in the body that pumps lethal doses of copper to fungi and bacteria shows promise as a new way to kill infectious microbes, a team of scientists at Duke University report. In a study published in the journal Chemistry & Biology, the researchers describe a way of exploiting the unique chemical response from the body’s immune system to attack pathogens using copper, long known for its antimicrobial properties, in a way that minimizes harm to the rest of the body.
The findings in cell and animal models represent progress in developing broad-spectrum antimicrobial agents on the basis of copper biology—a much-needed advance in the face of escalating antibiotic resistance and lethal fungal infections. Faced with fungal or bacterial infections, macrophages ingest and attempt to destroy the pathogens by locking them in tiny death chambers and unleashing an oxidative burst of hydrogen peroxide, nitric oxide and other poisons, including copper. But both fungi and bacteria deploy resistance mechanisms to the chemical onslaught in the macrophage compartments.
The scientists used a chemical trick that takes advantage of this oxidative onslaught to unleash the active molecule selectively in the 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 by avoiding copper binding in cells that have not been infected.
Senior author Dennis J. Thiele, PhD, says future studies will focus on enhancing the molecule’s drug-like properties to optimize its ability to fight additional fungal and bacterial infections in animal models. They are also continuing to explore how the molecule works, and whether related molecules can deliver additional metal payloads, including silver, which also has antimicrobial properties. Read the study abstract.
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