A new study on Legionnaires’ disease reveals new insights into the workings of the immune system and disease processes.
In 1976, shortly after the United States celebrated its bicentennial, a mysterious pneumonia-like disease took the lives of many war veterans after they attended the American Legion of Pennsylvania convention in Philadelphia.
After this first outbreak, the disease earned the name Legionnaires’ disease, which has been seeing a disturbing increase in cases lately.
A type of pneumonia, Legionnaires’ disease is a respiratory infection caused by naturally occurring bacteria in relatively hot stagnant water.
Infection occurs when an individual inhales small droplets of water contaminated by Legionella bacteria. Infections can cause complications ranging from mild fevers to death.
Fever, cough, muscle aches, headaches, and decreased appetite are the first symptoms of the Legionnaires’ disease. Although it can be fatal in some cases, particularly in the young and elderly.
The study on Legionnaires could potentially provide more effective treatments against the disease and other lethal infections.
The Immune System and Pathogens: the War of Proteins
The fight between the immune system and pathogenic bacteria is a battle of one-upmanship. For both sides, the main weapon is proteins.
In its continuous fight against harmful bacteria, the immune system relies on proteins. It relies on them either by calling on those stored in the body or synthesizing them on the spot.
Microorganisms also possess an arsenal of proteins that they unleash to subvert the immune system.
To flip the tables on these diseases, some researchers are investigating new treatment methods against pathogens.
A previous research from Walter and Eliza Hall Institute (Australia) has shown that a protein called BCL-XL is the “Achilles’ heel of Legionella-infected cells”.
Based on this, the team discovered that a class of drugs called BH3-mimetics. Although originally developed for cancer, these drugs can turn off BCL-XL and kill Legionella-infected cells.
Now, in a new study, biologists at Purdue University made another discovery about Legionella bacteria that could lead to a new treatment approach for bacterial infections.
“We have revealed an intricate mechanism of how a protein from the potentially deadly pathogen Legionella pneumophila turns off the major immune regulatory protein NF-κB, which controls numerous important cellular processes. This is important because it reveals a highly effective and specific way to turn off an immune response,” said Zhao-Qing Luo, who led the research.
Purdue researchers, who worked on Legionella pneumophila, found that a bacterial protein called MavC inhibits the action of UBE2N. This is a human protein that activates another major immune regulatory protein called NF-κB.
According to researchers, the countermove would be the development of proteins that inhibit the action of the bacterial enzyme.
The team thinks their findings pave the way to the development of novel antibiotics against bacterial infections. They also believe it could potentially help against autoimmune diseases.
“Further, because the bacterial enzyme effectively and highly specifically inhibits the activity of a human protein essential for immunity activation, another potential application avenue is to use it to suppress immunity for autoimmune diseases or other hyperinflammatory conditions. The major challenge in the latter application is the delivery of the genes to the patient, but the concept has been suggested by many scientists in the field.”
Full details of the study are published in the journal Nature Microbiology.