Compensatory evolution of Pseudomonas aeruginosa's slow growth phenotype suggests mechanisms of adaptation in cystic fibrosis

Long-term infection of the airways of cystic fibrosis patients with Pseudomonas aeruginosa is often accompanied by a reduction in bacterial growth rate. This reduction has been hypothesised to increase within-patient fitness and overall persistence of the pathogen. Here, we apply adaptive laboratory evolution to revert the slow growth phenotype of P. aeruginosa clinical strains back to a high growth rate. We identify several evolutionary trajectories and mechanisms leading to fast growth caused by transcriptional and mutational changes, which depend on the stage of adaptation of the strain. Return to high growth rate increases antibiotic susceptibility, which is only partially dependent on reversion of mutations or changes in the transcriptional profile of genes known to be linked to antibiotic resistance. We propose that similar mechanisms and evolutionary trajectories, in reverse direction, may be involved in pathogen adaptation and the establishment of chronic infections in the antibiotic-treated airways of cystic fibrosis patients.

Automated summary

Long-term infection with Pseudomonas aeruginosa in cystic fibrosis patients often leads to a reduction in bacterial growth rate. However, adaptive laboratory evolution can revert slow growth phenotype back to a high growth rate, increasing antibiotic susceptibility. This is achieved through evolutionary trajectories and mechanisms involving transcriptional and mutational changes, suggesting potential involvement in pathogen adaptation and chronic infections in antibiotic-treated patients with cystic fibrosis.