Featured Research

from universities, journals, and other organizations

Molecule enhances copper's lethal punch against microbes

Date:
July 31, 2014
Source:
Duke Medicine
Summary:
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, scientists report.

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 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.

"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 fungi 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 antimicrobial properties.

In addition to Thiele and Franz, study authors include Richard A. Festa and Marian E. Helsel.

The National Institutes of Health provided grant support (GM100678-02; GM007105-40; GM041840; AI106013; and GM084176).


Story Source:

The above story is based on materials provided by Duke Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. RichardA. Festa, MarianE. Helsel, KatherineJ. Franz, DennisJ. Thiele. Exploiting Innate Immune Cell Activation of a Copper-Dependent Antimicrobial Agent during Infection. Chemistry & Biology, 2014; DOI: 10.1016/j.chembiol.2014.06.009

Cite This Page:

Duke Medicine. "Molecule enhances copper's lethal punch against microbes." ScienceDaily. ScienceDaily, 31 July 2014. <www.sciencedaily.com/releases/2014/07/140731145500.htm>.
Duke Medicine. (2014, July 31). Molecule enhances copper's lethal punch against microbes. ScienceDaily. Retrieved September 30, 2014 from www.sciencedaily.com/releases/2014/07/140731145500.htm
Duke Medicine. "Molecule enhances copper's lethal punch against microbes." ScienceDaily. www.sciencedaily.com/releases/2014/07/140731145500.htm (accessed September 30, 2014).

Share This



More Health & Medicine News

Tuesday, September 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How 'Yes Means Yes' Defines Sexual Assault

How 'Yes Means Yes' Defines Sexual Assault

Newsy (Sep. 29, 2014) Aimed at reducing sexual assaults on college campuses, California has adopted a new law changing the standard of consent for sexual activity. Video provided by Newsy
Powered by NewsLook.com
Scientists May Have Found An Early Sign Of Pancreatic Cancer

Scientists May Have Found An Early Sign Of Pancreatic Cancer

Newsy (Sep. 29, 2014) Researchers looked at 1,500 blood samples and determined people who developed pancreatic cancer had more branched chain amino acids. Video provided by Newsy
Powered by NewsLook.com
Colo. Doctors See Cluster of Enterovirus Cases

Colo. Doctors See Cluster of Enterovirus Cases

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com
Dr.'s Unsure of Cause of Fast-Spreading Virus

Dr.'s Unsure of Cause of Fast-Spreading Virus

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins