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Pseudomonas aeruginosa aggregates in cystic fibrosis sputum produce exopolysaccharides that likely impede current therapies
Open accessAbstract
In cystic fibrosis (CF) airways, Pseudomonas aeruginosa forms cellular aggregates called biofilms that are thought to contribute to chronic infection. To form aggregates, P. aeruginosa can use different mechanisms, each with its own pathogenic implications. However, how they form in vivo is controversial and unclear. One mechanism involves a bacterially produced extracellular matrix that holds the aggregates together. Pel and Psl exopolysaccharides are structural and protective components of this matrix. We develop an immunohistochemical method to visualize Pel and Psl in CF sputum. We demonstrate that both exopolysaccharides are expressed in the CF airways and that the morphology of aggregates is consistent with an exopolysaccharide-dependent aggregation mechanism. We reason that the cationic exopolysaccharide Pel may interact with some of the abundant anionic host polymers in sputum. We show that Pel binds extracellular DNA (eDNA) and that this interaction likely impacts current therapies by increasing antimicrobial tolerance and protecting eDNA from digestion.
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“The mechanisms producing aggregation in vivo remain unclear, although it is unlikely that the depletion aggregation mechanism plays a critical role, as the specific aggregate structures created by this mechanism have not, so far, been observed in vivo105,106.”
From Pseudomonas aeruginosa: ecology, evolution, pathogenesis and antimicrobial susceptibility (2025) · cites this paper as [106]
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“Finally, biofilm aggregates in human chronic infections are surrounded by host immune cells106”
From Pseudomonas aeruginosa: ecology, evolution, pathogenesis and antimicrobial susceptibility (2025) · cites this paper as [106]
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Cited by
Microbial extracellular polymeric substances in the environment, technology and medicine
Flemming, H.-C., van Hullebusch, E. D., Little, B. J., Neu, T. R., Nielsen, P. H., Seviour, T., Stoodley, P., Wingender, J., & Wuertz, S. (2025) · Nature Reviews Microbiology · doi:10.1038/s41579-024-01098-y · Cited by 420
Gradients and consequences of heterogeneity in biofilms
Jo, J., Price-Whelan, A., & Dietrich, L. E. P. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00692-2 · Cited by 319
Pseudomonas 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
Therapeutic applications of curcumin nanomedicine formulations in cystic fibrosis
Quispe, C., Herrera-Bravo, J., Khan, K., Javed, Z., Semwal, P., Painuli, S., Kamiloglu, S., Martorell, M., Calina, D., & Sharifi-Rad, J. (2022) · Progress in Biomaterials · doi:10.1007/s40204-022-00198-3 · Cited by 26
Byeon, C., Kinney, T., Saricayir, H., Holst Hansen, K., Scott, F. J., Srinivasa, S., Wells, M. K., Mentink‐Vigier, F., Kim, W., & Akbey, Ü. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202418146 · Cited by 7
Metadata
- Authors
- Jennings, L. K., Dreifus, J. E., Reichhardt, C., Storek, K. M., Secor, P. R., Wozniak, D. J., Hisert, K. B., & Parsek, M. R.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 34
- Issue
- 8
- Pages
- 108782
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W3129883500
- Cited by
- 172
- References
- 0
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- gold
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- Jennings, L. K., Dreifus, J. E., Reichhardt, C., Storek, K. M., Secor, P. R., Wozniak, D. J., Hisert, K. B., & Parsek, M. R. (2021). Pseudomonas aeruginosa aggregates in cystic fibrosis sputum produce exopolysaccharides that likely impede current therapies. Cell Reports. https://doi.org/10.1016/j.celrep.2021.108782
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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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