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 How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>