Detection of bacterial extracellular vesicles in patients with cystic fibrosis - a pilot study

Celina von Mauch1, Lisa-Maria Edrich2, Julia Sobel3

  • 1Department of Pediatrics, Gastroenterology, Hepatology and Endoscopy, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Department of Medicine 1, Universitätsklinikum Erlangen, Erlangen, Germany.

Abstract

Insights

Bacterial extracellular vesicles (bEVs) are elevated in cystic fibrosis (CF) patients, particularly those with Pseudomonas aeruginosa infection. CFTR modulator treatment also impacts bEVs, suggesting a link to CF pathogenesis.

Area of Science:

  • Microbiology
  • Immunology
  • Pulmonology

Background:

  • Pseudomonas aeruginosa is an opportunistic pathogen frequently associated with Cystic Fibrosis (CF).
  • Bacterial extracellular vesicles (bEVs) accumulation in circulation is implicated in chronic inflammatory diseases.
  • bEVs show potential as diagnostic tools for various conditions.

Purpose of the Study:

  • To investigate the presence and activity of bEVs in plasma of individuals with CF.
  • To correlate bEV levels and activity with P. aeruginosa infection status in CF patients.
  • To explore the impact of CFTR modulator therapy on bEVs.

Main Methods:

  • Isolation and characterization of bEVs from plasma using Nanoparticle Tracking Analysis (NTA) and Transmission Electron Microscopy (TEM).
  • Analysis of bEVs in healthy controls (HC), CF patients without P. aeruginosa (PsA-), and CF patients with P. aeruginosa (PsA+).
  • Assessment of NF-κB induction via TLR4 reporter assay and correlation with clinical parameters and CFTR modulator treatment (ETI).

Main Results:

  • bEVs were detected in all study groups (HC, PsA-, PsA+).
  • Elevated NF-κB induction was observed in CF patients compared to HC, with the highest levels in PsA+ patients.
  • CFTR modulator treatment (ETI) increased bEV LPS concentration in CF patients, irrespective of P. aeruginosa colonization.

Conclusions:

  • Pulmonary P. aeruginosa colonization may be linked to increased systemic bEV activity in CF patients.
  • Deficient mucosal barrier function could contribute to elevated bEVs in CF.
  • Further research is needed to validate findings and understand ETI's influence on bEV accumulation.

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