Pf bacteriophage is associated with decline in lung function in a longitudinal cohort of patients with cystic fibrosis and Pseudomonas airway infection

• Published in: Journal of cystic fibrosis Vol. 24; no. 2; pp. 345 - 352
• Main Authors: Burgener, Elizabeth B., Gupta, Aditi, Nakano, Kayo, Gibbs, Sophia L., Sommers, Maya E., Khosravi, Arya, Bach, Michelle S., Dunn, Colleen, Spano, Jacquelyn, Secor, Patrick R., Tian, Lu, Bollyky, Paul L., Milla, Carlos E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2025
• Subjects: Adult; Bacteriophage; Bacteriophages - isolation & purification; Cross-Sectional Studies; Cystic Fibrosis - complications; Cystic Fibrosis - microbiology; Cystic Fibrosis - physiopathology; Female; Humans; Longitudinal Studies; Lung - physiopathology; Male; Pseudomonas; Pseudomonas aeruginosa - isolation & purification; Pseudomonas aeruginosa - virology; Pseudomonas Infections - diagnosis; Pseudomonas Infections - microbiology; Pseudomonas Infections - physiopathology; Pseudomonas Infections - virology; Pulmonary/Respiratory; Respiratory Function Tests - methods; Respiratory Tract Infections - microbiology; Sputum - microbiology; Sputum - virology; Pseudomonas; Bacteriophage
• ISSN: 1569-1993; 1873-5010; 1873-5010
• DOI: 10.1016/j.jcf.2024.09.018

•Pf bacteriophage of Pseudomonas aeruginosa is prevalent in sputum of people with cystic fibrosis.•Pf bacteriophage is associated with inflammatory and anti-viral cytokine response in the sputum.•High production of Pf bacteriophage is associated with greater loss of lung function over time.•Birefringent, liquid crystal structures are visualized in the airways of explanted lungs from subjects with known high production of Pf bacteriophage.•Pf bacteriophage is a potential prognostic biomarker and therapeutic target for chronic Pseudomoans aeruginosa infection. The Pseudomonas filamentous bacteriophage (Pf) infects Pseudomonas aeruginosa (Pa) and is abundant in the airways of many people with cystic fibrosis (CF) (pwCF). We previously demonstrated that Pf promotes biofilm growth, as well as generates liquid crystals that confer biofilms with adhesivity, viscosity and resistance to clearance. Consistent with these findings, the presence of Pf in sputum from pwCF has been linked to chronic Pa infection and more severe exacerbations in a cross-sectional cohort study. We examined the relationships between Pf and clinical outcomes in a longitudinal study of pwCF. Sputum Pa and Pf concentrations were measured by qPCR, as well cytokines and active neutrophil elastase by standardized assays. Recorded clinical data, including spirometry and microbiological results, were analyzed for associations with Pf. Finally, lung explants from pwCF in this cohort who underwent lung transplantation were examined for presence of liquid crystals within secretions. In explanted lungs from pwCF with known Pf infection we demonstrate areas of birefringence consistent with liquid crystalline structures within the airways. We find that high concentration of Pf in sputum is associated with accelerated loss of lung function, suggesting a potential role for Pf in the pathogenesis of CF lung disease. We also find Pf to associate with increased airway inflammation and an anti-viral cytokine response. Pf may serve as a prognostic biomarker and potential therapeutic target for Pa infections in CF.