Persistence and genetic adaptation of Pseudomonas aeruginosa in patients with Chronic Obstructive Pulmonary Disease

Objectives It is unclear whether recurrent sputum culture with P. aeruginosa from patients with chronic obstructive pulmonary disease (COPD) is caused by intermittent airway carriage by different P. aeruginosa lineages or persistent carriage by the same lineage, and if lineages genetically adapt during carriage. Methods Whole-genome sequencing of P. aeruginosa isolates sampled longitudinally from sputum cultures in COPD patients enrolled in an ongoing randomized controlled trial (Clinicaltrials.gov: NCT03262142). Results One-hundred and fifty-three P. aeruginosa isolates were sequenced in 23 patients during 365 days of follow-up. Recurrent presence of P. aeruginosa was seen in 19 (83%) patients and was caused by persistence of the same clonal lineage in all but one patient. We identified 38 genes mutated in parallel in two or more lineages, suggesting a positive selection for adaptive mutations. Mutational enrichment analysis revealed genes important for antibiotic resistance and chronic infections to be more frequently mutated. Conclusions Recurrent P. aeruginosa was common and carried for a prolonged time after the initial detection in the airways of patients with COPD. Recurrence was caused by persistence of the same clonal lineage and was associated with genetic adaptation. Trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in COPD is warranted.