Molecule enhances copper's lethal punch against microbes

July 31, 2014

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.

Publishing in the July 31, 2014, issue of 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 , 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 .

"There is a clear need for new strategies for antimicrobial therapies," said senior author Dennis J. Thiele, Ph.D., the George Barth Geller Professor
of Pharmacology and Cancer Biology and of Biochemistry at Duke University School of Medicine. "Copper, while essential, can be toxic when mismanaged by the body, but our work demonstrates that we can activate the metal's antimicrobial potential in a targeted fashion that focuses on the immune cells and avoids copper imbalance throughout the body."

Thiele, who has studied the biology of copper for more than 30 years, teamed with Katherine J. Franz, Ph.D., the Alexander F. Hehmeyer Associate Professor of Chemistry at Duke, to use a small molecule previously created in the Franz lab that essentially escorts additional copper to specialized chambers within immune cells called macrophages.

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 and bacteria deploy resistance mechanisms to the chemical onslaught in the macrophage compartments.

Thiele, Franz and colleagues used a clever 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.

"This provides a strategy for the development of compounds that exploit the activated immune response and override the copper detoxification machinery in fungal and bacterial pathogens to boost the body's own antimicrobial activity," Franz said.

Thiele said 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 .

Explore further: Antimicrobials: Silver (and copper) bullets to kill bacteria

Related Stories

Antimicrobials: Silver (and copper) bullets to kill bacteria

November 9, 2009

Dana Filoti of the University of New Hampshire will present thin films of silver and copper she has developed that can kill bacteria and may one day help to cut down on hospital infections. The antimicrobial properties of ...

Recommended for you

Basic research fuels advanced discovery

August 26, 2016

Clinical trials and translational medicine have certainly given people hope and rapid pathways to cures for some of mankind's most troublesome diseases, but now is not the time to overlook the power of basic research, says ...

New avenue for understanding cause of common diseases

August 25, 2016

A ground-breaking Auckland study could lead to discoveries about many common diseases such as diabetes, cancer and dementia. The new finding could also illuminate the broader role of the enigmatic mitochondria in human development.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.