Divergent, Coexisting XXXX Lineages in Chronic @entity82 .

@entity1 @entity82 @entity796 @entity281 @entity1577
RATIONALE: @entity796 , the predominant cause of chronic airway infections of @entity1 with @entity1577 , exhibits extensive phenotypic diversity among isolates within and between sputum samples, but little is known about the underlying genetic diversity. OBJECTIVES: To characterize the population genetic structure of transmissible @entity796 Liverpool Epidemic Strain in chronic infections of nine @entity1 with @entity1577 , and infer evolutionary processes associated with adaptation to the @entity82 . METHODS: We performed whole-genome sequencing of @entity796 isolates and pooled populations and used comparative analyses of genome sequences including phylogenetic reconstructions and resolution of population structure from genome-wide allele frequencies. MEASUREMENTS AND MAIN RESULTS: Genome sequences were obtained for 360 isolates from nine @entity1 . Phylogenetic reconstruction of the ancestry of 40 individually sequenced isolates from one @entity1 sputum sample revealed the coexistence of two genetically diverged, recombining lineages exchanging potentially adaptive mutations. Analysis of population samples for eight additional @entity1 indicated coexisting lineages in six cases. Reconstruction of the ancestry of individually sequenced isolates from all @entity1 indicated smaller genetic distances between than within @entity1 in most cases. CONCLUSIONS: Our population-level analysis demonstrates that coexistence of distinct lineages of @entity796 Liverpool Epidemic Strain within individuals is common. In several cases, coexisting lineages may have been present in the infecting inoculum or assembled through multiple transmissions. Divergent lineages can share mutations via homologous recombination, potentially aiding adaptation to the airway during @entity281 . The genetic diversity of this transmissible strain within infections, revealed by high-resolution genomics, has implications for @entity1 segregation and therapeutic strategies.
