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In cystic fibrosis (CF) patients, chronic airway infection by  Pseudomonas  leads to progressive lung destruction ultimately requiring lung transplantation (LT). Following LT, CF-adapted  Pseudomonas  strains, potentially originating from the sinuses, may seed the allograft leading to infections and reduced allograft survival. We investigated whether CF-adapted  Pseudomonas  populations invade the donor microbiota and adapt to the non-CF allograft. We collected sequential  Pseudomonas  isolates and airway samples from a CF-lung transplant recipient during two years, and followed the dynamics of the microbiota and  Pseudomonas  populations. We show that  Pseudomonas  invaded the host microbiota within three days post-LT, in association with a reduction in richness and diversity. A dominant mucoid and hypermutator  mutL  lineage was replaced after 11 days by non-mucoid strains. Despite antibiotic therapy,  Pseudomonas  dominated the allograft microbiota until day 95. We observed positive selection of pre-LT variants and the appearance of novel mutations. Phenotypic adaptation resulted in increased biofilm formation and swimming motility capacities.  Pseudomonas  was replaced after 95 days by a microbiota dominated by  Actinobacillus . In conclusion, mucoid  Pseudomonas  adapted to the CF-lung remained able to invade the allograft. Selection of both pre-existing non-mucoid subpopulations and of novel phenotypic traits suggests rapid adaptation of  Pseudomonas  to the non-CF allograft.

Rapid adaptation drives invasion of airway donor microbiota by Pseudomonas after lung transplantation