title: Bacterial evolution in PCD and CF patients follows the same mutational steps.
abstract: Infections with Pseudomonas aeruginosa increase morbidity in primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) patients. Both diseases are associated with a defect of the mucociliary clearance; in PCD caused by non-functional cilia, in CF by changed mucus. Whole genome sequencing of P. aeruginosa isolates from CF patients has shown that persistence of clonal lineages in the airways is facilitated by genetic adaptation. It is unknown whether this also applies to P. aeruginosa airway infections in PCD. We compared within-host evolution of P. aeruginosa in PCD and CF patients. P. aeruginosa isolates from 12 PCD patients were whole genome sequenced and phenotypically characterised. Ten out of 12 PCD patients were infected with persisting clone types. We identified convergent evolution in eight genes, which are also important for persistent infections in CF airways: genes related to antibiotic resistance, quorum sensing, motility, type III secretion and mucoidity. We document phenotypic and genotypic parallelism in the evolution of P. aeruginosa across infected patients with different genetic disorders. The parallel changes and convergent adaptation and evolution may be caused by similar selective forces such as the intensive antibiotic treatment and the inflammatory response, which drive the evolutionary processes.
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Hørsholm, Denmark.
authors.forename: Lea M
authors.initials: LM
authors.lastname: Sommer
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery and Audiology, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Mikkel Christian
authors.initials: MC
authors.lastname: Alanin
authors.affiliation: Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Denmark.|Center for Genomic Medicine, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Rasmus L
authors.initials: RL
authors.lastname: Marvig
authors.affiliation: Danish PCD Centre, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Kim Gjerum
authors.initials: KG
authors.lastname: Nielsen
authors.affiliation: Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Denmark.|Institute of Immunology and Microbiology, University of Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Høiby
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery and Audiology, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: von Buchwald
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Hørsholm, Denmark.|Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Molin
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Hørsholm, Denmark.|Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Helle Krogh
authors.initials: HK
authors.lastname: Johansen
mesh_terms: D003550:Cystic Fibrosis / Q000235:genetics / Q000382:microbiology*; D019143:Evolution, Molecular; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D007619:Kartagener Syndrome / Q000235:genetics / Q000382:microbiology*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011552:Pseudomonas Infections / Q000235:genetics*; D011550:Pseudomonas aeruginosa / Q000235:genetics*