Featured Research

from universities, journals, and other organizations

Defense mechanism against bacteria and fungi deciphered

Date:
January 22, 2011
Source:
Technische Universitaet Muenchen
Summary:
To defend microbial attacks, the human body naturally produces a group of antibiotics, called defensins. An interdisciplinary team of biochemists and medical scientists has now deciphered the mechanism of action of a defensin, hitherto looked upon as exhibiting only minor activity. Their results might be useful in future drug development for inflammatory and infectious diseases. Nature now presents their findings online ahead of the print publication.

Surprisingly, while almost all proteins are active only in their folded form, in the case of the small defensin the opposite is true. To activate the beta-defensin 1 the thioredoxin opens the three disulphide bridges that hold the molecule together. The molecule then opens up into the active state. Using this mechanism the body has the opportunity to selectively activate the defensin.
Credit: TUM

To defend microbial attacks, the human body naturally produces a group of antibiotics, called defensins. An interdisciplinary team of biochemists and medical scientists has now deciphered the mechanism of action of a defensin, hitherto looked upon as exhibiting only minor activity. Their results might be useful in future drug development for inflammatory and infectious diseases. Nature now presents their findings online ahead of the print publication.

Under standard laboratory conditions, the human beta-defensin 1 (hBD-1), a human antibiotic naturally produced in the body, had always shown only little activity against microbes. Nevertheless the human body produces it in remarkable quantities. The solution to the puzzle was the investigation process itself, as the research group led by Dr. Jan Wehkamp at the Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology of the Stuttgart-based Robert Bosch Hospital found out.

Before the research group took a new approach to this research, defensins were usually tested in the presence of oxygen, although little oxygen is present, for example, in the human intestine. Starting out from the discovery that a special antibiotic-activating protein of the human body is diminished in patients with inflammatory bowel diseases, Crohn's Disease and Ulcerative Colitis, the working group investigated how defensins act under low-oxygen conditions. During their investigations the scientists found out that under these conditions hBD-1 unfolds a strong antibiotic activity against lactic acid bacteria and yeast.

Furthermore the researchers discovered that another human protein, thioredoxin, is able to activate beta-defensin 1 even in the presence of oxygen. Moritz Marcinowski and Professor Johannes Buchner from the Department of Chemistry at the Technical University of Munich, used circular dichroism spectroscopy to elucidate the differences between the folded inactive and the unfolded active form of the protein.

Surprisingly, while almost all proteins are active only in their folded form, in the case of the small defensin the opposite is true. To activate the beta-defensin 1 the thioredoxin opens the three disulphide bridges that hold the molecule together. The molecule then opens up into the active state. Using this mechanism the body has the opportunity to selectively activate the defensin.

So far the cause of inflammatory bowel disease is unclear. Genetic as well as environmental factors seem to play a role, finally leading to a weakening of the antimicrobial barrier, which is mainly mediated by defensins. Accordingly the identified mechanism might contribute to the development of new therapies to treat affected patients.

The presented work is the result of a cooperation project with six participating centers, led by Emmy Noether junior research group leader Dr. Jan Wehkamp. In addition to five researchers from Stuttgart (Dr. Margarete Fischer-Bosch-Institute for Clinical Pharmacology and the Robert Bosch-Hospital (Bjoern Schroeder, Sabine Nuding, Julia Beisner, Eduard Stange and Jan Wehkamp) the Department of Dermatology at University of Tόbingen (Martin Schaller), the Max-Planck-Institute for Developmental Biology in Tόbingen (Sandra Groscurth), the Department of Dermatology at University of Kiel (Zhihong Wu), as well as the Department of Chemistry at the Technische Universitaet Muenchen (Moritz Marcinowski and Johannes Buchner) were involved. The work was funded by the Deutsche Forschungsgemeinschaft (Emmy Noether-Program for young researchers, Cluster of Excellence Center for Integrated Protein Science Munich) and by the Robert- Bosch-Foundation.


Story Source:

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


Journal Reference:

  1. Bjoern O. Schroeder, Zhihong Wu, Sabine Nuding, Sandra Groscurth, Moritz Marcinowski, Julia Beisner, Johannes Buchner, Martin Schaller, Eduard F. Stange, Jan Wehkamp. Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1. Nature, 2011; 469 (7330): 419 DOI: 10.1038/nature09674

Cite This Page:

Technische Universitaet Muenchen. "Defense mechanism against bacteria and fungi deciphered." ScienceDaily. ScienceDaily, 22 January 2011. <www.sciencedaily.com/releases/2011/01/110121144003.htm>.
Technische Universitaet Muenchen. (2011, January 22). Defense mechanism against bacteria and fungi deciphered. ScienceDaily. Retrieved August 27, 2014 from www.sciencedaily.com/releases/2011/01/110121144003.htm
Technische Universitaet Muenchen. "Defense mechanism against bacteria and fungi deciphered." ScienceDaily. www.sciencedaily.com/releases/2011/01/110121144003.htm (accessed August 27, 2014).

Share This




More Health & Medicine News

Wednesday, August 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

WHO Calls for Ban on E-Cigarette Sales to Minors

WHO Calls for Ban on E-Cigarette Sales to Minors

AFP (Aug. 26, 2014) — The World Health Organization called Tuesday on governments should ban the sale of e-cigarettes to minors, warning that they pose a "serious threat" to foetuses and young people. Duration: 01:44 Video provided by AFP
Powered by NewsLook.com
Have You Ever Been 'Sleep Drunk?' 1 in 7 Has

Have You Ever Been 'Sleep Drunk?' 1 in 7 Has

Newsy (Aug. 26, 2014) — A study published in the journal "Neurology" interviewed more than 19,000 people and found 15 percent suffer from being "sleep drunk." Video provided by Newsy
Powered by NewsLook.com
Does Medical Marijuana Reduce Painkiller Overdose Deaths?

Does Medical Marijuana Reduce Painkiller Overdose Deaths?

Newsy (Aug. 26, 2014) — A new study found fewer deaths from prescription drug overdoses in states that have legalized medical marijuana. But experts disagree on the results. Video provided by Newsy
Powered by NewsLook.com
Official: British Ebola Sufferer Receiving Experimental Drug

Official: British Ebola Sufferer Receiving Experimental Drug

AFP (Aug. 26, 2014) — A British nurse infected with Ebola while working in Sierra Leone is being given the same experimental drug used on two US missionaries who have recovered for the disease, doctors in London say. Duration: 00:44 Video provided by AFP
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:
from the past week

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