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: firstname.lastname@example.org
Diana Yates | University of Illinois
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction