Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients
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In many human infections, hosts and pathogens coexist for years or decades. Important examples include HIV, herpes viruses, tuberculosis, leprosy, and malaria. With the exception of intensively studied viral infections such as HIV/AIDs, little is known about the extent to which the clonal expansion that occurs during long-term infection by pathogens involves important genetic adaptations. We report here a detailed, whole-genome analysis of one such infection, that of a cystic fibrosis (CF) patient by the opportunistic bacterial pathogen Pseudomonas aeruginosa . The bacteria underwent numerous genetic adaptations during 8 years of infection, as evidenced by a positive-selection signal across the genome and an overwhelming signal in specific genes, several of which are mutated during the course of most CF infections. Of particular interest is our finding that virulence factors that are required for the initiation of acute infections are often selected against during chronic infections. It is apparent that the genotypes of the P. aeruginosa strains present in advanced CF infections differ systematically from those of “wild-type” P. aeruginosa and that these differences may offer new opportunities for treatment of this chronic disease.
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Bacterial pathogens accumulate mutations to compete with resident microbiome and host factors when entering the host intestines.
“Extensive studies proved bacterial pathogens accumulate mutations to compete with resident microbiome and host factors when entering the host intestines.23,24”
From Gut microbiota drives structural variation of exogenous probiotics to enhance colonization (2025) · cites this paper as [23]
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- Authors
- Smith, E. E., Buckley, D. G., Wu, Z., Saenphimmachak, C., Hoffman, L. R., D’Argenio, D. A., Miller, S. I., Ramsey, B. W., Speert, D. P., Moskowitz, S. M., Burns, J. L., Kaul, R., & Olson, M. V.
- Affiliations
- University of Washington (US)
- **Division of Infectious and Immunological Diseases, Department of Pediatrics, British Columbia Research Institute for Children’s and Women’s Health, 950 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-05-30
- Volume
- 103
- Issue
- 22
- Pages
- 8487-8492
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1482519
- OpenAlex
- W1979152503
- Cited by
- 1,319
- References
- 39
- Citations by year
- 2026: 40 · 2025: 41 · 2024: 34 · 2023: 54 · 2022: 65 · 2021: 73 · 2020: 65 · 2019: 68 · 2018: 51 · 2017: 74 · 2016: 80 · 2015: 72 · 2014: 85 · 2013: 80 · 2012: 78
- FWCI
- 54.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Washington
- National Institutes of Health
- National Heart, Lung, and Blood Institute (K08HL067903)
- National Human Genome Research Institute (P50HG002351)
- National Institute of Diabetes and Digestive and Kidney Diseases (1R01 DK 64954-01A1, R01DK064954)
- National Center for Research Resources (M01RR000037)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- Pseudomonas aeruginosa, cystic fibrosis, chronic bacterial infection, host-pathogen coevolution, positive selection, whole genome sequencing, virulence genes, clonal expansion, opportunistic bacterial infection, airway colonization
- MeSH terms
- Adaptation, Physiological, Bacterial Proteins, Chronic Disease, Cystic Fibrosis, DNA-Binding Proteins, Humans, Molecular Sequence Data, Mutation, Pseudomonas aeruginosa, Pseudomonas Infections, Selection, Genetic, Time Factors, Trans-Activators, Genome, Bacterial
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