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Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs
Open accessAbstract
Summary Bacterial lineages that chronically infect cystic fibrosis (CF) patients genetically diversify during infection. However, the mechanisms driving diversification are unknown. By dissecting 10 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 type 3 secretion systems. 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.
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Cited by
Pseudomonas aeruginosa: An Audacious Pathogen with an Adaptable Arsenal of Virulence Factors
Jurado-Martín, I., Sainz-Mejías, M., & McClean, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22063128 · Cited by 698
Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium
Bryant, J. M., Grogono, D. M., Rodriguez-Rincon, D., Everall, I., Brown, K. P., Moreno, P., Verma, D., Hill, E., Drijkoningen, J., Gilligan, P., et al. (2016) · Science · doi:10.1126/science.aaf8156 · Cited by 587
Hisert, K. B., Heltshe, S. L., Pope, C., Jorth, P., Wu, X., Edwards, R. M., Radey, M., Accurso, F. J., Wolter, D. J., Cooke, G., et al. (2017) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201609-1954oc · Cited by 389
Self-citationPseudomonas aeruginosa: ecology, evolution, pathogenesis and antimicrobial susceptibility
Letizia, M., Diggle, S. P., & Whiteley, M. (2025) · Nature Reviews Microbiology · doi:10.1038/s41579-025-01193-8 · Cited by 231
Selective pressures during chronic infection drive microbial competition and cooperation
Baishya, J., & Wakeman, C. A. (2019) · npj Biofilms and Microbiomes · doi:10.1038/s41522-019-0089-2 · Cited by 70
Metadata
- Authors
- Jorth, P., Staudinger, B. J., Wu, X., Hisert, K. B., Hayden, H., Garudathri, J., Harding, C. L., Radey, M. C., Rezayat, A., Bautista, G., Berrington, W. R., Goddard, A. F., Zheng, C., Angermeyer, A., Brittnacher, M. J., Kitzman, J., Shendure, J., Fligner, C. L., Mittler, J., Aitken, M. L., Manoil, C., Bruce, J. E., Yahr, T. L., & Singh, P. K.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 18
- Issue
- 3
- Pages
- 307-319
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W1802199068
- Cited by
- 306
- References
- 0
- FWCI
- 24.50
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs. https://app.cochat.ai/papers/10.1016/j.chom.2015.07.006
- The paper
- Jorth, P., Staudinger, B. J., Wu, X., Hisert, K. B., Hayden, H., Garudathri, J., Harding, C. L., Radey, M. C., Rezayat, A., Bautista, G., Berrington, W. R., Goddard, A. F., Zheng, C., Angermeyer, A., Brittnacher, M. J., Kitzman, J., Shendure, J., Fligner, C. L., Mittler, J., . . . Singh, P. K. (2015). Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs. Cell Host & Microbe. https://doi.org/10.1016/j.chom.2015.07.006
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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