Persistence and genetic adaptation of Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease

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  • Josefin Eklöf
  • Maria A. Misiakou
  • Pradeesh Sivapalan
  • Karin Armbruster
  • Andrea Browatzki
  • Thyge L. Nielsen
  • Therese S. Lapperre
  • Helle F. Andreassen
  • Migle Gabrielaite
  • Annemette Jensen
  • Tine V. Nielsen
  • Khaled Ghathian
  • Henrik Calum
  • Niels Seersholm
  • Rasmus L. Marvig

Objectives: It is unclear whether recurrent sputum culture with Pseudomonas 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 whether lineages genetically adapt during carriage. Methods: Whole-genome sequencing was performed for P. aeruginosa isolates sampled longitudinally from sputum cultures in patients with COPD who were enrolled in an ongoing randomized controlled trial (clinicaltrials.gov: NCT03262142). Results: A total of 153 P. aeruginosa isolates were sequenced for 23 patients during 365 days of follow-up. Recurrent presence of P. aeruginosa was seen in 19 patients (83%) 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 positive selection for adaptive mutations. Mutational enrichment analysis revealed genes important in antibiotic resistance and chronic infections to be more frequently mutated. Discussion: Recurrent P. aeruginosa was common and carried for a prolonged time after 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 are warranted.

OriginalsprogEngelsk
TidsskriftClinical Microbiology and Infection
Vol/bind28
Udgave nummer7
Sider (fra-til)990-995
Antal sider6
ISSN1198-743X
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
This work was supported by grants from The Independent Research Fund Denmark (grant number 8020-00425B) and the research committee at the Copenhagen University Hospital-Herlev and Gentofte Hospital. MG and RLM are supported by the Danish National Research Foundation (grant number 126). The research salary of PS was sponsored by the Copenhagen University Hospital-Herlev and Gentofte Hospital. The foundations had no role in the design, implementation, interpretation, or reporting of the study. None of the authors have any conflicts of interest that are directly related to this work.

Funding Information:
This work was supported by grants from The Independent Research Fund Denmark (grant number 8020-00425B ) and the research committee at the Copenhagen University Hospital-Herlev and Gentofte Hospital . MG and RLM are supported by the Danish National Research Foundation (grant number 126 ). The research salary of PS was sponsored by the Copenhagen University Hospital-Herlev and Gentofte Hospital . The foundations had no role in the design, implementation, interpretation, or reporting of the study. None of the authors have any conflicts of interest that are directly related to this work.

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© 2022 The Author(s)

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