CHICAGO, March 25 (Xinhua) -- Researchers at the University of Illinois (UI) and Mie University in Japan found a bacterial protein fragment instigates lung tissue death in pulmonary fibrosis, a mysterious disease affecting millions of people worldwide, according to a news release posted on UI's website on Tuesday.
Previous studies found that certain bacteria, such as strains of Halomonas, Staphylococcus and Streptococcus, proliferate in the lungs of idiopathic pulmonary fibrosis (IPF) patients, likely as a result of high amounts of salt in the lining of patients' lungs. So the researchers cultured bacteria associated with fibrotic lung tissue in a salty environment and studied what the bacteria secreted.
They found a small peptide, secreted by Staphylococcus nepalensis, that rapidly kills lung cells. They named the peptide corisin.
To confirm that corisin was the exacerbating culprit, the researchers ran an experiment on mice with IPF. They compared mice given corisin itself, those infected with corisin-secreting Staphylococcus nepalensis, those infected with a Staph strain that did not secrete corisin, and an untreated control group, and found that the mice given corisin or the bacterium that secretes it showed much greater signs of acute exacerbation, a phase when a patient experiences a rapid worsening of breathing and loss of lung function.
The researchers also looked at lung tissue samples from human patients and found that those who had undergone acute exacerbation had higher levels of corisin in their lungs.
The researchers then searched the genome of Staphylococcus nepalensis to figure out where corisin comes from. They found that it is a fragment cut from a larger protein. They tested the larger protein on lung tissue and found it did not have the destructive properties of the fragment.
"It's like a Trojan horse," said UI microbiology and animal sciences professor Isaac Cann. "Anybody trying to characterize the large protein to find what it does would never know it has this destructive element hidden inside it. The microbe makes the polypeptide and then it cuts out that small piece of it, the corisin, and that is very deadly."
The findings may have important implications for the prevailing coronavirus pandemic, as some patients may develop pulmonary fibrosis after recovering from COVID-19, in similarity to the fibrosis seen in some patients after the outbreak of the SARS coronavirus, the researchers noted.
In the next step, the researchers hope to identify the enzyme that cuts corisin out of its larger protein. They aim to create agents to block it. They also plan to identify which other strains of bacteria produce corisin or similar peptides, and to study other types of fibrosis, such as in the kidneys and liver, to see if corisin or other bacterial agents play a role in those diseases.
In people with pulmonary fibrosis, lung tissue becomes progressively more scarred and stiffened, with a prognosis of only three to five years of life after diagnosis. About 50,000 patients in the United States die of IPF every year, more than those who die from breast cancer, according to the IPF Foundation.
The findings have been published in the journal Nature Communications.