Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Anthrax paralyzes immune cells with lethal toxin

08.05.2007
University of Florida researchers have revealed how the inhaled form of anthrax paralyzes the body's defenses and prevents immune cells from reaching the site of infection.

Anthrax killed five people in 2001 when letters containing the bacteria's spores were sent through the mail. The UF findings, published last week in the EMBO Journal, may lead to quicker diagnoses for anthrax victims.

The disease causes flu-like symptoms that can take weeks to develop, according to the Centers for Disease Control and Prevention. But once the first symptom appears, the disease progresses rapidly and patients often die from shock before they realize they have more than a common cold. The current method of detecting anthrax relies on lab cultures that can take days to complete.

"We're looking for approaches to detect anthrax earlier in the blood," said Russell During, Ph.D., a postdoctoral fellow at UF's College of Medicine. "We're trying to develop a test that would allow detection within two or three hours of the bugs entering the blood and secreting toxins."

... more about:
»Anthrax »Listeria »Southwick »Toxin »immune »lethal »paralyze

Once inhaled, anthrax releases a lethal toxin that immobilizes the white blood cells that normally seek and destroy invading bacteria. Just traces of the toxin can slow movement of these cells, called neutrophils, by 50 percent, UF researchers discovered.

"Neutrophils have to get to the infection to kill anything. If you paralyze them so they don't move, they can't protect you," said Fred Southwick, M.D., division chief of infectious diseases at the UF College of Medicine and the study's lead author.

But exactly how the anthrax toxin wards off neutrophils has puzzled scientists for years. Immune cells rely on rod-shaped filaments called actin to propel them toward an infection. In a previous study, Southwick found that the toxin prevents actin assembly, leaving neutrophils stuck in the mud.

"Actin is important because it's the motor that causes neutrophils to move," said Southwick. "So it's like cutting the gas to the motor."

Anthrax literally cuts the gas line. The toxin works like a pair of scissors, snipping off the ends of a key protein and preventing the transmission of messages within the cell. As a result, immune cells never receive the green light to assemble the actin motor, Southwick's findings demonstrate.

"Together, these studies provide important clues about how anthrax escapes the immune system during infection," said Nick Duesbery, Ph.D. deputy director for research operations and senior scientific investigator at the Van Andel Institute in Grand Rapids, Mich.

In 1998, Duesbery discovered that the toxin interrupts the transmission of signals within cells. But Dr. Southwick's study is the first to explain how anthrax can short-circuit a cell signal to block neutrophil movement, a realization that has eluded scientists for years. The finding almost escaped Southwick's research team as well, which was looking for proteins that interacted directly with the toxin.

"I would say it's the scientific equivalent of finding a needle in a haystack," Southwick said.

The team compared before and after snapshots of neutrophils exposed to a purified form of the toxin, as well as images showing how protein expression changed in cells. After scrutinizing the images for hours, During finally identified one protein that seemed to disappear upon exposure to anthrax. The protein turned out to be responsible for gathering the components of actin and shuttling them to the center of the cell, where they are assembled into filaments.

"We've discovered that through this pathway, lethal toxin blocks the function of a protein that regulates how actin assembles," said Southwick, who believes his findings may also explain how anthrax paralyzes other types of cells, like the platelets that normally help blood clot.

"We know that patients with anthrax bleed," Southwick said, adding that victims of inhalational anthrax often suffer hemorrhages in their lungs and lymph nodes. "No one understands why, and it could very well be due to paralysis of platelets." During and Southwick are currently looking for additional proteins targeted by anthrax. They hope to develop a diagnostic blood test that detects the bacterium by checking for telltale changes in protein expression.

Southwick's team used an unusual approach to tease out the anthrax toxin's effects on cell migration: They allowed the immune cells to be hijacked by another bacterium, Listeria monocytogenes. Listeria is often used as a tool to study actin because it commandeers human cells and induces them to form the filaments, which the bacteria use to navigate around the body.

"We used one bacterium to weed out another. I'm not aware of anyone ever doing that," Southwick said. "In an individual cell, you can't figure out where the actin is assembling and what's controlling it. But Listeria seems to use the same pathways that a cell uses to crawl. So anything that blocks Listeria we predict would also block neutrophils from crawling. And that's what we found."

Ann Griswold | EurekAlert!
Further information:
http://www.ufl.edu

Further reports about: Anthrax Listeria Southwick Toxin immune lethal paralyze

More articles from Life Sciences:

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Underwater acoustic localization of marine mammals and vehicles

23.11.2017 | Information Technology

Enhancing the quantum sensing capabilities of diamond

23.11.2017 | Physics and Astronomy

Meadows beat out shrubs when it comes to storing carbon

23.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>