title: Rapid adaptation drives invasion of airway donor microbiota by Pseudomonas after lung transplantation.
abstract: 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.
authors.affiliation: Service of Infectious Diseases, University Hospitals of Geneva and Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Beaume
authors.affiliation: Service of Infectious Diseases, University Hospitals of Geneva and Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Köhler
authors.affiliation: Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.|Service of Infectious Diseases, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Greub
authors.affiliation: Service of Infectious Diseases, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.|Transplantation Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Manuel
authors.affiliation: Transplantation Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.|Service of Pulmonary Diseases, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: J-D
authors.initials: JD
authors.lastname: Aubert
authors.affiliation: Fasteris SA, Plan-les-Ouates, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Baerlocher
authors.affiliation: Fasteris SA, Plan-les-Ouates, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Farinelli
authors.affiliation: ESI &CEC, Biosciences, University of Exeter, Penryn Campus, Cornwall, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Buckling
authors.affiliation: Service of Infectious Diseases, University Hospitals of Geneva and Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: van Delden
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D064591:Allografts; D015169:Colony Count, Microbial; D003550:Cystic Fibrosis / Q000382:microbiology; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D008168:Lung / Q000382:microbiology*; D016040:Lung Transplantation; D064307:Microbiota; D010641:Phenotype; D011549:Pseudomonas / Q000302:isolation & purification / Q000502:physiology*; D014019:Tissue Donors