By IDSE News Staff
A virus that infects a common bacterium may lead to accelerated loss of lung function in people with cystic fibrosis (CF), according to a study by researchers at Children’s Hospital Los Angeles (CHLA).
The researchers found that a high concentration of Pseudomonas aeruginosa infected with the Pseudomonas filamentous bacteriophage (Pf phage) in sputum is associated with persistent airway inflammation and infection among CF patients (J Cyst Fibros 2024 Oct 25. doi:10.1016/j.jcf.2024.09.018).
“This study suggests that Pf phage may be a useful prognostic biomarker that could identify patients at risk for rapid decline, and signal the need for early and aggressive interventions,” said Elizabeth Burgener, MD, the associate director of the Cystic Fibrosis Foundation Therapeutics Development Center for CHLA, and lead author of the study.
People with CF experience progressive declines in lung function, often leading to respiratory failure and premature death. In recent years, CF transmembrane conductance regulator (CFTR) modulator therapies have dramatically improved patient outcomes. However, many patients still develop chronic, treatment-resistant Pseudomonas infections in their airways.
The lung function is worse during a CF exacerbation if their sputum has Pf phase versus if it does not, according to Dr. Burgener, who is also a pediatric pulmonologist in pulmonology and sleep medicine at CHLA. “We wanted to follow patients over time and see if lung function deteriorated more quickly if they had both Pseudomonas and Pf phage in their sputum,” she said.
In this latest six-year study, Dr. Burgener and her team measured the relationships between Pf phage and clinical outcomes of 121 adults and children with CF. In addition to finding that Pf phage in sputum was associated with reduced lung function over time, the team also found a greater inflammatory and antiviral response. She noted that increased inflammatory cytokines could trigger more mucous secretion and impair clearance of mucus leading to further tissue damage.
“While we did not see increased mortality or incidence of lung transplant during the study period between groups, we did see an accelerated loss of lung function in those with the highest sputum concentrations of Pf phage compared to the concentration of Pseudomonas,” Dr. Burgener said.
Although most phages kill bacteria, the Pf phage is different. It appears to reinforce the biofilm surrounding the Pseudomonas bacteria. “That’s one of the ways that Pseudomonas persists in chronic infection in the lungs, in wounds, in patients with tracheostomies or ventilator tubes,” Dr. Burgener said. “This long, skinny filamentous phage organizes the biofilm polymers in the airway into liquid crystals.”
In another recent study, Dr. Burgener’s team found that when the Pf phage was present, the cilia were less effective (PNAS Nexus 2024;3[9]:390 https://doi.org/10.1093/pnasnexus/pgae390). The Pf phage entangled the cilia, tamping them down like a trampled shag rug, although it didn’t change the frequency of the ciliary beating. In CF cell cultures and piglet tracheas, adding the Pf phage decreased the velocity of mucous transport. In CF cell cultures, the Pf phage also prevented mucous clearance even when the cultures were pretreated with CFTR modulator medications.
Dr. Burgener’s lab is now examining the antibiotic tolerance provided by the PF phage and its relation to the development of antibiotic resistance.
