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

Cell Rep. 2021 Feb 23;34(8):108782. doi: 10.1016/j.celrep.2021.108782.

Abstract

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.

Keywords: IHC; Pel; Pseudomonas aeruginosa biofilm matrix; Psl; antibiotic susceptibility; bacterial aggregation; biofilm; cystic fibrosis; exopolysaccharide; extracellular DNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Biofilms / growth & development
  • Cystic Fibrosis / drug therapy
  • Cystic Fibrosis / microbiology*
  • DNA, Bacterial / genetics
  • DNA, Bacterial / metabolism
  • Drug Resistance, Bacterial
  • Expectorants / therapeutic use
  • Humans
  • Lung / microbiology*
  • Polysaccharides, Bacterial / metabolism*
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / microbiology*
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / metabolism*
  • Respiratory Tract Infections / drug therapy
  • Respiratory Tract Infections / microbiology*
  • Sputum / microbiology

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • Expectorants
  • Polysaccharides, Bacterial
  • exopolysaccharide, Pseudomonas