Researchers have identified a naturally occurring lipid – a waxy, fatty acid – used by a disease-causing bacterium to impair the host immune response and increase the chance of infection.
According to the researchers, including Schwarz B from the National Institutes of Health (NIH) in Hamilton, inadvertently, they may have found a potent inflammation therapy against bacterial and viral diseases.
Lipids are known to help Francisella tularensis bacteria – the cause of tularemia – to suppress host inflammation when infecting mouse and human cells.
The findings, published in the Journal of Innate Immunity, found a form of the lipid Phosphatidylethanolamine, or PE, present in the bacterium.
The composition of PE found in F. tularensis differs from PE found in other bacteria. In cell-culture experiments, the researchers discovered that the natural and a synthetic form of PE reduced inflammation caused by both tularemia bacteria and dengue fever virus.
Tularemia is a life-threatening disease spread to humans via contact with an infected animal or through the bite of a mosquito, tick or deer fly.
Although tularemia can be successfully treated with antibiotics, it is difficult to diagnose, mainly because Francisella tularensis bacteria can suppress the human immune response, the researchers said.
Dengue fever, primarily spread by Aedes aegypti mosquitoes, is rarely fatal but usually leads to a high fever, severe headache and pain throughout the body. There is no specific treatment for dengue fever, they added.
The researchers, after identifying PE as the lipid that impaired the immune response, began to consider its potential therapeutic value. Because natural Francisella tularensis is highly infectious and therefore challenging to work with, the group developed synthetic lipids – PE2410 and PEPC2410 – that would be much easier to study and produce.
The researchers then verified that both synthetic lipids also suppressed the immune response during infection of mouse and human cells in the laboratory. Both versions inhibited the immune response compared to the immune response seen in infected but untreated cells, the researchers said.