Adaptation and genomic erosion in fragmented Pseudomonas aeruginosa populations in the sinuses of people with cystic fibrosis
Catherine R. Armbruster,
Christopher W. Marshall,
Arkadiy I. Garber,
Jeffrey A. Melvin,
Anna C. Zemke,
John Moore,
Paula F. Zamora,
Kelvin Li,
Ian L. Fritz,
Christopher D. Manko,
Madison L. Weaver,
Jordan R. Gaston,
Alison Morris,
Barbara Methé,
William H. DePas,
Stella E. Lee,
Vaughn S. Cooper,
Jennifer M. Bomberger
Affiliations
Catherine R. Armbruster
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
Christopher W. Marshall
Department of Biological Sciences, Marquette University, Milwaukee, WI 53233, USA
Arkadiy I. Garber
Biodesign Center for Mechanisms of Evolution and School of Life Sciences, Arizona State University, Tempe, AZ 85281, USA
Jeffrey A. Melvin
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
Anna C. Zemke
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
John Moore
Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA
Paula F. Zamora
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
Kelvin Li
Center for Medicine and the Microbiome, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA
Ian L. Fritz
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
Christopher D. Manko
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
Madison L. Weaver
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
Jordan R. Gaston
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
Alison Morris
Center for Medicine and the Microbiome, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA
Barbara Methé
Center for Medicine and the Microbiome, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA
William H. DePas
Department of Pediatrics, Children’s Hospital of Pittsburgh and University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
Stella E. Lee
Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA; Corresponding author
Vaughn S. Cooper
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; Center for Medicine and the Microbiome, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA; Pittsburgh Center for Evolutionary Biology & Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; Corresponding author
Jennifer M. Bomberger
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; Corresponding author
Summary: 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.
