title: Global and local selection acting on the pathogen Stenotrophomonas maltophilia in the human lung.
abstract: Bacterial populations diversify during infection into distinct subpopulations that coexist within the human body. Yet, it is unknown to what extent subpopulations adapt to location-specific selective pressures as they migrate and evolve across space. Here we identify bacterial genes under local and global selection by testing for spatial co-occurrence of adaptive mutations. We sequence 552 genomes of the pathogen Stenotrophomonas maltophilia across 23 sites of the lungs from a patient with cystic fibrosis. We show that although genetically close isolates colocalize in space, distant lineages with distinct phenotypes separated by adaptive mutations spread throughout the lung, suggesting global selective pressures. Yet, for one gene (a distant homologue of the merC gene implicated in metal resistance), mutations arising independently in two lineages colocalize in space, providing evidence for location-specific selection. Our work presents a general framework for understanding how selection acts upon a pathogen that colonizes and evolves across the complex environment of the human body.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Hattie
authors.identifier: 0000-0001-8417-5606
authors.initials: H
authors.lastname: Chung
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Tami D
authors.initials: TD
authors.lastname: Lieberman
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Sara O
authors.initials: SO
authors.lastname: Vargas
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Kelly B
authors.initials: KB
authors.lastname: Flett
authors.affiliation: Department of Laboratory Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: McAdam
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA.|Division of Critical Care Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Gregory P
authors.identifier: 0000-0001-9831-0354
authors.initials: GP
authors.lastname: Priebe
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.|Faculty of Biology, Technion Israel Institute of Technology, Haifa 32000, Israel.|Faculty of Computer Science, Technion Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Roy
authors.initials: R
authors.lastname: Kishony
mesh_terms: D003550:Cystic Fibrosis / Q000382:microbiology; D006801:Humans; D008168:Lung / Q000382:microbiology*; D010802:Phylogeny; D012641:Selection, Genetic; D020615:Stenotrophomonas maltophilia / Q000235:genetics*