An investigation led by the University of Pittsburgh School of Medicine has found a link between a new class of bacterial enzymes and the chronic lung inflammation that plagues patients with cystic fibrosis, a terminal lung disease characterized by excess mucus buildup in the body.
The study, published Monday by the Proceedings of the National Academy of Sciences, details that the bacteria, P. aeruginosa, thrives in inflamed lungs, secreting an enzyme called Cif that sabotages the body’s ability to make a key molecule called a “pro-resolving lipid mediator,” which helps halt inflammation.
Researchers confirmed this mechanism by analyzing lung secretions from cystic fibrosis patients seen at Children’s Hospital of Pittsburgh of UPMC and linking their findings to patient records. Patients with higher Cif levels in their lung secretions experienced less signaling to stop inflammation and increased levels of IL-8, a marker for inflammation. Increased Cif levels were also linked to reduced lung function.
“There are about 30,000 patients in the U.S. with cystic fibrosis, and hundreds of thousands more with other chronic lung diseases. Once these diseases progress to the point that the patient is chronically infected with P. aeruginosa, current antimicrobial therapies are no longer effective and there are very few treatment options left,” said Jennifer M. Bomberger, assistant professor in Pitt’s Department of Microbiology & Molecular Genetics and senior author on the study, in a statement. “Lung damage from these chronic P. aeruginosa infections, coupled with a robust but unproductive inflammatory response to the infection, will eventually lead to respiratory failure in the patient and the need for a lung transplant.”