Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study Finds Anthrax Toxins Also Harmful To Fruit Flies

31.01.2006


Deadly and damaging toxins that allow anthrax to cause disease and death in mammals have similar toxic effects in fruit flies, according to a study conducted by biologists at the University of California, San Diego.


Photo shows effect of anthrax lethal factor toxin in dorsal cells of developing fruit fly larvae. Credit: Annabel Guichard, UCSD



Their findings, which appear this week in an early online edition of the journal Proceedings of the National Academy of Sciences, show that fruit flies can be used to study the link between the biochemical activities and physiological effects of anthrax toxins.

Learning how these toxins attack developing and adult tissues is important because it can help scientists understand how they function at the molecular level and may lead to new therapeutic strategies for neutralizing their effects in humans.


Annabel Guichard, a biologist at UCSD and lead author of the study, tracked the ways that two active anthrax toxins, known as lethal factor, or LF, and edema factor, EF, cause cellular damage and death in the fruit fly Drosophila melanogaster. These toxins are required for the anthrax bacterium Bacillus anthracis to evade the host immune system and cause disease.

Using a combination of biochemical, genetic and cell biological approaches, the biologists tested whether or not the anthrax toxins were active in living Drosophila and, if so, whether they acted in the same way as they do in humans. The biologists found that anthrax toxins do alter the same signaling pathways used for cell communication in fruit flies and humans.

“Drosophila is an excellent tool to understand the effect of a toxin on its host and to determine the molecular mechanism underlying its toxicity, because the fly system is already so well characterized,” Guichard said. “We knew how anthrax toxins acted on human cells, but this study is the first to show that these toxins are active in fruit flies, suggesting that this fast breeding laboratory animal could also be used to determine the function of a variety of bacterial and viral pathogenic factors.”

Anthrax bacterium secretes three toxins, including LF and EF, and is only known to infect mammals. Because fruit flies lack components required for toxin entry into cells, they cannot actually contract the anthrax disease. However, the study finds that fruit flies can be used to test the effects of a single virulence factor, such as the LF or EF toxins, on signaling pathways shared by flies and humans.

Guichard and her co-authors applied lethal factor toxin to fruit fly embryos and larvae and observed that a component of the expected signaling pathway was inactivated, disrupting the whole molecular system and leading to death. When applied in a more limited fashion, LF interfered with the formation of sutures in the epidermis, resulting in a hole or cleft in thoracic regions of embryos and adults. This developmental process disrupted by LF treatment is similar mechanistically to wound healing, which is mediated by the same signaling pathway in humans.

The EF toxin is also lethal when applied to fly larvae and can cause severe malformation in the wings of adult fruit flies—an effect that can also be understood as an interruption of another unrelated signaling process common to flies and humans.

“We asked the simple question of whether anthrax toxins affecting mammals could act on the fly counterparts of proteins affected in humans, and the answer is yes,” said Ethan Bier, a professor of biology at UCSD who was the senior author of the study. “What this means is that similar types of analyses might identify yet unknown proteins shared by flies and humans that can be acted on by anthrax toxins. More generally, this study suggests that flies can be used as a rapid whole organism system to determine the function of a variety of bacterial and viral pathogens of unknown function. One could then test hypotheses obtained from these studies with flies in mammalian organisms such as mice.”

The biologists also anticipate that toxins such as the anthrax lethal factor toxin that have multiple host target proteins may be used to simultaneously reduce or eliminate the activities of several related proteins that perform overlapping functions in other diseases or biological processes. Such experimental tools could accelerate progress in various areas of biomedical research.

Guichard first conceived this study in 2002, to apply her experience in molecular genetic studies to research that had medical application. At that time, after the spate of anthrax-laced letters in 2001, anthrax became a charged topic in the research community and the general public.

“Anthrax is still a hot subject because of its possible use as a weapon of bioterrorism and remains a health threat in third world countries,” Guichard said. “Anthrax infections can be cured by antibiotics when detected early. But after a certain point, the toxins released in the bloodstream can kill the patient even after antibiotic treatment. The more we understand about how the toxins function, the better we’ll be able to design effective co-operative or “adjunctive” therapies.”

Other contributors to this study were Michael Karin in the department of pharmacology at UCSD’s School of Medicine, Jin Mo Park, now at Harvard Medical School and Beatriz Cruz-Moreno at UCSD. The study was supported by grants from the National Institutes of Health.

Media Contact: Kim McDonald (858) 534-7572.

Comments: Annabel Guichard (858) 534-0442, or Ethan Bier (858) 534-8792.

Kim McDonald | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Colorectal cancer risk factors decrypted
13.07.2018 | Max-Planck-Institut für Stoffwechselforschung

nachricht Algae Have Land Genes
13.07.2018 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Research finds new molecular structures in boron-based nanoclusters

13.07.2018 | Materials Sciences

Algae Have Land Genes

13.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>