Lab technician using microscope.
(photo credit: INGIMAGE / ASAP)
Hebrew University researchers have shown for the first time how bacterial superantigen toxins work and how short peptides can block them and save lives. With major implications for medicine, their novel approach is both broad-acting and impervious to bacterial antibiotic resistance.
Every year, staphylococcal and streptococcal infections affect millions of individuals and are the leading cause of sepsis, accounting for many cases of pneumonia and post-surgical infections.
Despite the urgency of this situation, pharmaceutical companies are not developing a lot of new antibiotics because of the high cost of research and a low return. Multi-drug resistance to existing antibiotics is rampant, rendering the classical one-bug, one-drug approach obsolete.
The ability of staphylococcal and streptococcal bacteria to cause disease is due to numerous virulence factors, among which a group called superantigens play a prominent role.
Several dozen superantigens are highly lethal in humans and are critical contributors to sepsis and progression to toxic shock.
While the inflammatory immune response is essential to protecting humans against viruses and bacteria, superantigen toxins cause an exaggerated response – called an “immune storm” – that can do a great deal of damage in the body and can lead to multiple organ failure. Even with currently available treatment strategies, most of these diseases have high death rates.
Complicating treatment of these bacterial infections are multi-drug resistant strains.
Prof. Raymond Kaempfer, who specializes in molecular biology and cancer research as a part of HU’s Institute for Medical Research Israel- Canada (IMRIC), and colleagues have produced what is described as “landmark” research paper, which was published Monday in the Proceedings of the National Academy of Sciences, and is based on 20 years of scientific investigation.
The researchers show for the first time how bacterial superantigen toxins work and how antagonists they designed can block toxin action and save patients. They used a novel host-oriented therapeutic approach for preventing lethal immune responses.
“Rather than targeting the bacterial pathogens, which can then mutate to develop antibiotic resistance, host-oriented therapeutics have the advantage of remaining effective even against infections with antibiotic-resistant strains.
This is because, before the pathogens can cause severe disease, they must also pass through the same receptor bottleneck in the immune response, which we can block effectively.”