Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs
| Autor: | Angus Angermeyer, Xia Wu, Corinne L. Fligner, Benjamin J. Staudinger, Jayanthi Garudathri, Peter Jorth, Hillary S. Hayden, John E. Mittler, Pradeep K. Singh, Matthew C. Radey, William R. Berrington, Timothy L. Yahr, Mitchell J. Brittnacher, Colin Manoil, Gilbert E. Bautista, Jacob O. Kitzman, Moira L. Aitken, Amanda F. Goddard, James E. Bruce, Amir Rezayat, Katherine B. Hisert, Jay Shendure, Christopher L. Harding, Chunxiang Zheng |
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| Rok vydání: | 2015 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Cancer Research Cystic Fibrosis Molecular Sequence Data Virulence Biology medicine.disease_cause Microbiology Cystic fibrosis Type three secretion system 03 medical and health sciences Antibiotic resistance Immunology and Microbiology(all) Virology medicine Humans Pseudomonas Infections Molecular Biology Lung Pathogen 030304 developmental biology Genetics 0303 health sciences 030306 microbiology Pseudomonas aeruginosa Genetic Variation Sequence Analysis DNA medicine.disease Divergent evolution medicine.anatomical_structure Immunology Parasitology |
| Zdroj: | Cell Host & Microbe. 18:307-319 |
| ISSN: | 1931-3128 |
| DOI: | 10.1016/j.chom.2015.07.006 |
| Popis: | SummaryBacterial lineages that chronically infect cystic fibrosis (CF) patients genetically diversify during infection. However, the mechanisms driving diversification are unknown. By dissecting ten CF lung pairs and studying ∼12,000 regional isolates, we were able to investigate whether clonally related Pseudomonas aeruginosa inhabiting different lung regions evolve independently and differ functionally. Phylogenetic analysis of genome sequences showed that regional isolation of P. aeruginosa drives divergent evolution. We investigated the consequences of regional evolution by studying isolates from mildly and severely diseased lung regions and found evolved differences in bacterial nutritional requirements, host defense and antibiotic resistance, and virulence due to hyperactivity of the type 3 secretion system. These findings suggest that bacterial intermixing is limited in CF lungs and that regional selective pressures may markedly differ. The findings also may explain how specialized bacterial variants arise during infection and raise the possibility that pathogen diversification occurs in other chronic infections characterized by spatially heterogeneous conditions. |
| Databáze: | OpenAIRE |
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