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.
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: email@example.com
Diana Yates | University of Illinois
Closing the carbon loop
08.12.2016 | University of Pittsburgh
Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
08.12.2016 | Life Sciences
08.12.2016 | Physics and Astronomy
08.12.2016 | Materials Sciences