Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Convergent evolution and adaptation of Pseudomonas aeruginosa within patients with cystic fibrosis

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. The genetic evolution of metastatic uveal melanoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Primary ciliary dyskinesia patients have the same P. aeruginosa clone in sinuses and lungs

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Filamentous bacteriophages are associated with chronic Pseudomonas lung infections and antibiotic resistance in cystic fibrosis

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Little is known about how within-host evolution compares between genotypically different strains of the same pathogenic species. We sequenced the whole genomes of 474 longitudinally collected clinical isolates of Pseudomonas aeruginosa sampled from 34 children and young individuals with cystic fibrosis. Our analysis of 36 P. aeruginosa lineages identified convergent molecular evolution in 52 genes. This list of genes suggests a role in host adaptation for remodeling of regulatory networks and central metabolism, acquisition of antibiotic resistance and loss of extracellular virulence factors. Furthermore, we find an ordered succession of mutations in key regulatory networks. Accordingly, mutations in downstream transcriptional regulators were contingent upon mutations in upstream regulators, suggesting that remodeling of regulatory networks might be important in adaptation. The characterization of genes involved in host adaptation may help in predicting bacterial evolution in patients with cystic fibrosis and in the design of future intervention strategies.

Original languageEnglish
JournalNature Genetics
Volume47
Issue number1
Pages (from-to)57-64
Number of pages8
ISSN1061-4036
DOIs
Publication statusPublished - Jan 2015

    Research areas

  • Adaptation, Biological, Adolescent, Adult, Bacterial Proteins, Carrier State, Child, Child, Preschool, Clone Cells, Cystic Fibrosis, Evolution, Molecular, Female, Follow-Up Studies, Gene Expression Regulation, Bacterial, Gene Regulatory Networks, Genes, Bacterial, Genome, Bacterial, Host-Pathogen Interactions, Humans, Infant, Male, Molecular Sequence Data, Mutation, Phylogeny, Polymorphism, Single Nucleotide, Pseudomonas Infections, Pseudomonas aeruginosa, Respiratory System, Signal Transduction, Sputum, Virulence, Young Adult

ID: 45102978