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
Division of Pediatric Pulmonology and Sleep Medicine, Children's Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA; Center for Excellence in Pulmonary Biology, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
Center for Excellence in Pulmonary Biology, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
J Cyst Fibros. 2025 Mar;24(2):345-352. doi: 10.1016/j.jcf.2024.09.018. Epub 2024 Oct 25.
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.
铜绿假单胞菌丝状噬菌体（Pf）感染铜绿假单胞菌（Pa），且在许多囊性纤维化（CF）患者（pwCF）的气道中大量存在。我们之前证明，Pf可促进生物膜生长，并产生赋予生物膜粘附性、粘性和抗清除性的液晶。与这些发现一致，在一项横断面队列研究中，pwCF痰液中Pf的存在与慢性Pa感染及更严重的病情加重有关。
我们在一项针对pwCF的纵向研究中检测了Pf与临床结局之间的关系。通过qPCR测量痰液中Pa和Pf的浓度，同时通过标准化检测测量细胞因子和活性中性粒细胞弹性蛋白酶。分析记录的临床数据，包括肺功能测定和微生物学结果，以确定与Pf的关联。最后，对该队列中接受肺移植的pwCF患者的肺组织进行检查，以确定分泌物中是否存在液晶。
在已知感染Pf的pwCF患者的移植肺中，我们发现气道内存在与液晶结构一致的双折射区域。我们发现痰液中高浓度的Pf与肺功能加速丧失有关，这表明Pf在CF肺部疾病的发病机制中可能发挥作用。我们还发现Pf与气道炎症增加和抗病毒细胞因子反应有关。
Pf可能是CF患者Pa感染的预后生物标志物和潜在治疗靶点。
