4.8 Article

Pseudomonas aeruginosa aggregates in cystic fibrosis sputum produce exopolysaccharides that likely impede current therapies

Journal

CELL REPORTS
Volume 34, Issue 8, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2021.108782

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Funding

  1. NIH [5R01AI077628, R01AI143916, R01AI134895]
  2. CFF [PARSEK17IO, REICHH19F5]
  3. AHA fellowship [14POST20130017]
  4. NIH K99 [5K99GM134121-02]
  5. [P20GM103546]
  6. [R01AI138981]

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In cystic fibrosis airways, Pseudomonas aeruginosa forms biofilms that are thought to contribute to chronic infection. Exopolysaccharides Pel and Psi are expressed in CF airways and play a role in the aggregation mechanism, potentially impacting therapies by increasing antimicrobial tolerance and protecting extracellular DNA from digestion.
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 Psi exopolysaccharides are structural and protective components of this matrix. We develop an immunohistochemical method to visualize Pel and Psi 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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