From the Journals

Filamentous bacteriophage linked to lung infections in patients with cystic fibrosis



Filamentous bacteriophage (Pf phage) may contribute to Pseudomonas aeruginosa infections in cystic fibrosis (CF) patients, according to a study of the prevalence and clinical relevance of Pf phage in two patient cohorts.

CDC/ Janice Haney Carr

A number of Pseudomonas aeruginosa bacteria.

“Our data from both the Stanford and Danish CF cohorts together suggest that either patients with CF acquire Pf phage–producing strains of P. aeruginosa or the Pf phage–negative P. aeruginosa become infected with Pf phage as patients age and their disease progresses,” wrote Elizabeth B. Burgener, MD, of Stanford (Calif.) University, and her coauthors. The study was published in Science Translational Medicine.The study analyzed a previous Danish longitudinal cohort of 34 patients and a prospective cross-sectional cohort of 76 patients at Stanford, 58 of which had P. aeruginosa. The researchers also reviewed a collection of genetic sequences called the Pseudomonas Genome Database to determine the prevalence of Pf phage, finding evidence in 1,159 of 2,226 P. aeruginosa sequences (52.1%).

In the Danish cohort, 21 of the 34 CF patients (61.8%; 95% confidence interval, 43.6%-77.8%) had at least one P. aeruginosa isolate containing Pf phage; 9 (26.5%) of the patients were found to be consistently positive for Pf phage. Those who were consistently positive were also older than those who never had Pf phage detected (19.1 years vs. 13.9 years; P = .046), suggesting that “there may be a tendency for P. aeruginosa strains that produce Pf phage to dominate in the sputum of individual patients with CF over time.”

In the Stanford cohort, the prevalence of Pf phage was 36.2% (21 of 58; 95% CI, 24.0%-49.9%) in patients with P. aeruginosa infection and 27.6% (21 of 76; 95% CI, 18.0%-39.1%) in all patients. No Pf phage was detected in any P. aeruginosa–negative samples. Patients positive for Pf phage in this cohort were also older than patients who were negative.

The authors acknowledged their study’s limitations, describing the methods used to collect and sequence the analyzed samples as “highly heterogeneous.” In addition, the two cohorts were CF specific while the Genome Database is not. Finally, the CF cohorts only had a single dominant strain sampled, though multiple P. aeruginosa lineages are often present in CF patients.

One author reported receiving grants from the Cystic Fibrosis Foundation, clinical trial support, and consulting fees from industry. Two other authors are inventors on a patent application that covers the development of a vaccine that targets Pf phage. The others reported no conflicts of interest.

SOURCE: Burgener EB et al. Sci Transl Med. 2019 Apr 17. doi: 10.1126/scitranslmed.aau9748.

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