Dynamic genetic structure of Pseudomonas aeruginosa in transmissible chronic infections of cystic fibrosis airways

Pseudomonas aeruginosa chronic infections of cystic fibrosis (CF) airways are a paradigm for within-host evolution with abundant evidence for rapid evolutionary adaptation and diversification. Recently emerged transmissible strains have spread globally, with the Liverpool Epidemic Strain (LES) the most common strain infecting the UK CF population. However, despite its clinical importance, little is known about the impact of transmissibility on the genetic structure of these infections over time. To characterise this, we longitudinally sampled a meta-population of 15 LES lineages over 13 months among seven chronically infected CF patients by genome sequencing. Comparative genome analyses of P. aeruginosa populations revealed highly dynamic within-patient population genetic structure, including shifts in the relative abundance of lineages and rapid replacement of dominant lineages, likely to represent super-infection of diverged lineages by repeated transmissions. Lineage dynamics within patients led to rapid changes in the frequencies of mutations across suites of linked loci carried by each lineage. Many of these loci were associated with important infection phenotypes such as antibiotic resistance, mucoidy and quorum sensing, and were repeatedly and independently mutated in different lineages. These findings suggest that transmissibility leads to rapid shifts in the genetic structure of CF infections, including in clinically important phenotypes, and is likely to impede accurate diagnosis and treatment.