Pseudomonas aeruginosa microevolution during chronic infection of the CF lung

The airways of most cystic fibrosis patients get colonised with Pseudomonas aeruginosa bacteria in childhood or adolescence. In many cases the bacteria are able to establish a chronic infection whose course is a major determinant of the patient’s clinical status and quality of life. The infecting P. aeruginosa strains can display highly divergent phenotypes, which go along with high genomic variability, as 10 – 20 % of the genomic DNA is specific for clonal lineages or even single isolates. Furthermore, the strains acquire mutations during chronic infection which are hypothesized to cause additional phenotypical changes involved in facilitating persistence and adaptation to the CF lung habitat. To analyse the genetic background of strains having established a chronic infection and the following microevolution in the CF lung we performed genome sequencing for sequential isolates from 12 patients’ airways. For all patients, chronic infection was indicated by the presence of an individual clonal lineage over years. Isolates from six patients with a mild and six with a severe clinical course were studied reflecting infection periods of six to nearly 25 years. The genome of the first isolate of a persisting clone was analysed for its clone specific variations and accessory genome compared to the P. aeruginosa reference strain PA14. Then the genomic variations appearing by the later isolates were determined to analyse the microevolution that appeared during the chronic infection and to define hotspots of mutations that are typical for the process of adaptation to the CF lung.