Persistence and genetic adaptation of Pseudomonas aeruginosa in patients with COPD

Background: Pulmonary P. aeruginosa infections increase morbidity in COPD patients. While low resolution molecular typing has shown that the same clonal lineage can persist and adapt in the lungs, the prevalence of chronic infections in consistently sampled COPD cohorts remains unknown. Objective: The study aim was to determine the prevalence and genetic adaptation of persistent P. aeruginosa infections in patients with COPD. Methods: Whole-genome sequencing study of P. aeruginosa strains sampled longitudinally from sputum cultures in 23 patients enrolled in an ongoing randomized controlled trial in Denmark (clinicaltrials.gov: NCT03262142). Results: A total of 153 P. aeruginosa isolates were sequenced in 23 patients during 365 days of follow-up. Genome sequencing showed that 18 patients were infected with clonal lineages that persisted for at least 30 days (Figure 1). We identified 37 P. aeruginosa genes that were independently mutated in two or more lineages, suggesting a positive selection for adaptive mutations. Mutation in the same genes have previously been shown to be important for persistent infections in patients with genetically defined mucociliary clearance defects. Conclusion:P. aeruginosa persists and genetically adapts in patients with COPD. Thus, our results indicate parallelism to P. aeruginosa infections in patients with genetically defined mucociliary clearance defects.