Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Engineered protein effective against Staphylococcus aureus toxin

22.05.2007
A research team led by the University of Illinois has developed a treatment for exposure to enterotoxin B, a noxious substance produced by the Staphylococcus aureus bacterium. The team engineered a protein, which was successfully tested in rabbits, that could one day be used to treat humans exposed to the enterotoxin.

S. aureus enterotoxin B (SEB) is a common cause of food poisoning, but if it is inhaled or produced during an infection it can elicit a systemic – and sometimes fatal – immune response in humans. In purified form, SEB is listed as a potential bioterrorism agent. Other potent S. aureus enterotoxins include the toxic shock syndrome toxin.

These enterotoxins are classed as superantigens because they set off a massive immune response in humans and other animals. They bind to variable regions of T-cell receptors, stimulating a cascade of events, including the systemic release of inflammatory cytokines. In some cases the powerful immune response leads to toxic shock and death.

The research team, led by U. of I. professor of biochemistry David M. Kranz, included scientists and clinicians from the Boston Biomedical Research Institute and the University of Minnesota Medical School. Their findings appear today in the online edition of Nature Medicine.

... more about:
»SEB »Toxin »aureus »enterotoxin »immune »immune response

The team began by engineering a protein with the same structure as the binding site of the T-cell receptor targeted by SEB. The researchers expressed the engineered protein on the surface of yeast cells (using a process they helped develop, called “yeast display”) and generated mutations meant to increase the protein's ability to bind SEB. After several rounds of mutagenesis and screening, graduate student Rebecca A. Buonpane developed a soluble protein with an affinity for SEB that was over a million times that of the original.

“Our approach was to take these receptors that bind to the toxins and to try to make them higher affinity and therefore act as effective neutralizing agents when delivered in soluble form,” Kranz said. “It’s the binding of the toxin to T-cells that is critical. If you can prevent the toxin from binding to the T-cell receptor then you can prevent it from initiating that cascade.”

The engineered protein prevented the onset of symptoms in rabbits exposed to SEB and reversed the course of the illness in those treated two hours after exposure.

“We were very pleasantly surprised that it showed effectiveness in every rabbit tested,” Kranz said.

He noted that the protein has some potential advantages and disadvantages when compared to antibodies, which might also be used to fight infection with SEB. One advantage is that the engineered protein is small, about 1/10th the size of an antibody. Its size may allow it to penetrate deeper into tissues, and may make it less likely to spark an immune response in animals. The protein can also be produced in large quantities using the bacterium, Escherichia coli.

“E. coli is the cheapest source for making proteins,” Kranz said. “Whenever you can express a protein in E. coli you do so because it is inexpensive, easy and fast.”

Antibodies, on the other hand, can remain in the body for days or weeks, whereas the new protein is cleared within hours. This may make antibodies a better treatment option in some circumstances, Kranz said.

No antibody has yet been developed, however, that has a comparable affinity for SEB.

These studies were supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

Kranz is also affiliated with the Institute for Genomic Biology and the College of Medicine. Biochemistry at the U. of I. is in the School of Molecular and Cellular Biology.

Editor’s note: To reach David M. Kranz, call 217-244-2821; e-mail: d-kranz@uiuc.edu

Diana Yates | University of Illinois
Further information:
http://www.uiuc.edu

Further reports about: SEB Toxin aureus enterotoxin immune immune response

More articles from Life Sciences:

nachricht Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen

nachricht New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Unraveling the nature of 'whistlers' from space in the lab

15.08.2018 | Physics and Astronomy

Diving robots find Antarctic winter seas exhale surprising amounts of carbon dioxide

15.08.2018 | Earth Sciences

Early opaque universe linked to galaxy scarcity

15.08.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>