Genomics of Diversification of Pseudomonas aeruginosa in Cystic Fibrosis Lung-like Conditions.

Abstract

Pseudomonas aeruginosa is among the most problematic opportunistic pathogens for adults with cystic fibrosis (CF), causing repeated and resilient infections in the lung and surrounding airways. Evidence suggests that long-term infections are associated with diversification into specialized types but the underlying cause of that diversification and the effect it has on the persistence of infections remains poorly understood. Here, we use evolve-and-resequence experiments to investigate the genetic changes accompanying rapid, de novo phenotypic diversification in lab environments designed to mimic two aspects of human lung ecology: spatial structure and complex nutritional content. After ∼220 generations of evolution, we find extensive genetic variation present in all environments, including those that most closely resemble the CF lung. We use the abundance and frequency of nonsynonymous and synonymous mutations to estimate the ratio of mutations that are selectively neutral (hitchhikers) to those that are under positive selection (drivers). A significantly lower proportion of driver mutations in spatially structured populations suggests that reduced dispersal generates subpopulations with reduced effective population size, decreasing the supply of beneficial mutations and causing more divergent evolutionary trajectories. In addition, we find mutations in a handful of genes typically associated with chronic infection in the CF lung, including one gene associated with antibiotic resistance. This demonstrates that many of the genetic changes considered to be hallmarks of CF lung adaptation can arise as a result of adaptation to a novel environment and do not necessarily require antimicrobial treatment, immune system suppression, or competition from other microbial species to occur.