Adaptation and genomic erosion in fragmented Pseudomonas aeruginosa populations in the sinuses of people with cystic fibrosis.

Pseudomonas aeruginosa notoriously adapts to the airways of people with cystic fibrosis (CF), yet how infection-site biogeography and associated evolutionary processes vary as lifelong infections progress remains unclear. Here we test the hypothesis that early adaptations promoting aggregation influence evolutionary-genetic trajectories by examining longitudinal P. aeruginosa from the sinuses of six adults with CF. Highly host-adapted lineages harbored mutator genotypes displaying signatures of early genome degradation associated with recent host restriction. Using an advanced imaging technique (MiPACT-HCR [microbial identification after passive clarity technique]), we find population structure tracks with genome degradation, with the most host-adapted, genome-degraded P. aeruginosa (the mutators) residing in small, sparse aggregates. We propose that following initial adaptive evolution in larger populations under strong selection for aggregation, P. aeruginosa persists in small, fragmented populations that experience stronger effects of genetic drift. These conditions enrich for mutators and promote degenerative genome evolution. Our findings underscore the importance of infection-site biogeography to pathogen evolution. [Display omitted] • Selection favors P. aeruginosa mutations that promote aggregation in the CF sinuses • Aggregation and bottlenecks fragment populations, amplifying effects of genetic drift • Mutators persist in small populations and drive early genome degradation • Population size and infection-site biogeography impact evolutionary trajectories Armbruster et al. find that infection-site biogeography impacts evolution of the opportunistic pathogen, Pseudomonas aeruginosa. In the sinuses of adults with cystic fibrosis, P. aeruginosa residing in large, dense aggregates adaptively evolves, whereas small, sparse aggregates experience greater effects of genetic drift and early stages of degenerative genome evolution. [ABSTRACT FROM AUTHOR]