Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UW researchers find second anthrax toxin receptor

08.04.2003


Building on their 2001 discovery of a cellular doorway used by anthrax toxin to enter cells, University of Wisconsin Medical School researchers have found a second anthrax toxin doorway, or receptor. The finding could offer new clues to preventing the toxin’s entrance into cells.

The researchers also have found that when they isolated a specific segment of the receptor in the laboratory, they could use it as a decoy to lure anthrax toxin away from the real cell receptors, preventing much of the toxin from entering cells and inflicting its usually fatal damage.

The findings will appear in this week’s (the week of April 7) online "Early Edition" of the Proceedings of the National Academy of Sciences (http://www.pnas.org).



The new details on the way anthrax toxin enters cells should provide pharmaceutical companies with important new ammunition to attack the grave problem of anthrax disease, says lead researcher John A. T. Young, the Howard M. Temin Professor of Cancer Research at the Medical School’s McArdle Laboratory for Cancer Research.

"This discovery gives scientists more tools to understand how the anthrax toxin works," says Young, adding that he and his team were very surprised to find the second receptor, since the prevailing theory had been that only one exists. Heather Scobie, G. Jonah Rainey and Kenneth Bradley were team members and co-authors on the paper.

The existence of two receptors makes it clear that the toxin’s entry into cells is much more complicated than previously thought, notes Young, an expert on receptor molecules.

Scientists do know that to prevent anthrax disease, antibiotics must be administered immediately to kill anthrax bacteria that typically enter the body as spores via the skin, lungs or gastrointestinal tract. Once activated, the spores become bacteria and soon release toxins consisting of three components.

One toxic component, protective antigen (PA), must attach, or bind, to a receptor before the rest of the toxin can enter cells. Once attached, PA transports the other components - edema factor and lethal factor - into the cells, where they produce effects that can lead quickly to devastating disease symptoms.

Following their 2001 discovery of anthrax toxin receptor (ATR), the UW researchers worked with a protein that has similar molecular features. They chose the protein - called human capillary morphogenesis protein 2, or CMG2 - because it contains an important segment that is somewhat similar to that found in ATR. The segment is the part of the molecule that attaches directly to PA.

"We thought we would use CMG2 as a starting point to make genetic changes to find which characteristics of ATR are important to receptor binding," says Young. "To our surprise, we found that CMG2 itself is an anthrax toxin receptor."

The occurrence of multiple receptors - on the same or different cells - is not uncommon, says Young, citing HIV as an example of a pathogen that employs two major co-receptors to enter cells.

The existence of the two anthrax toxin receptors should interest cancer researchers, as both receptors are turned on when new blood vessels are forming - a process called angiogenesis, Scobie says.

"This may explain anthrax toxin’s effectiveness in treating cancer, which has been shown in studies by other scientists," she adds. "The toxin may have prevented the development of tumor-promoting angiogenesis."

In their previous work, Young and his colleagues used a laboratory-made version of the specific ATR segment that attaches to anthrax toxin as a decoy, and found it to be successful in preventing the toxin from entering the cell. Performing the same exercise with CMG2, they found the new decoy even more effective at enticing the toxin away from the real receptor.

"The new decoy is remarkably potent," says Rainey. "With a ratio of three parts CMG2 decoy to one part toxin, we found that we could effectively neutralize the toxin. Much more of the ATR decoy was required to be effective."

Young said his team now is trying to understand why the new decoy works better.

"We are trying to further improve its function. Our hope is that an improved form of the decoy could be used therapeutically," he says.

The research is supported by a grant from the National Institute of Allergy and Infectious Diseases.


- Dian Land, (608) 263-9893, dj.land@hosp.wisc.edu


John Young | University of Wisconsin-Madison
Further information:
http://www.news.wisc.edu/releases/view.html?id=8477&month=Apr&year=2003

More articles from Life Sciences:

nachricht Oestrogen regulates pathological changes of bones via bone lining cells
28.07.2017 | Veterinärmedizinische Universität Wien

nachricht Programming cells with computer-like logic
27.07.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Abrupt motion sharpens x-ray pulses

Spectrally narrow x-ray pulses may be “sharpened” by purely mechanical means. This sounds surprisingly, but a team of theoretical and experimental physicists developed and realized such a method. It is based on fast motions, precisely synchronized with the pulses, of a target interacting with the x-ray light. Thereby, photons are redistributed within the x-ray pulse to the desired spectral region.

A team of theoretical physicists from the MPI for Nuclear Physics (MPIK) in Heidelberg has developed a novel method to intensify the spectrally broad x-ray...

Im Focus: Physicists Design Ultrafocused Pulses

Physicists working with researcher Oriol Romero-Isart devised a new simple scheme to theoretically generate arbitrarily short and focused electromagnetic fields. This new tool could be used for precise sensing and in microscopy.

Microwaves, heat radiation, light and X-radiation are examples for electromagnetic waves. Many applications require to focus the electromagnetic fields to...

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

New 3-D imaging reveals how human cell nucleus organizes DNA and chromatin of its genome

28.07.2017 | Health and Medicine

Heavy metals in water meet their match

28.07.2017 | Power and Electrical Engineering

Oestrogen regulates pathological changes of bones via bone lining cells

28.07.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>