Pyocyanin and 1-hydroxyphenazine produced by Pseudomonas aeruginosa inhibit the beating of human respiratory cilia in vitro

J Clin Invest. 1987 Jan;79(1):221-9. doi: 10.1172/JCI112787.

Abstract

Pseudomonas aeruginosa culture filtrates varied in their ability to slow human ciliary beat frequency (7-71%). This activity did not correlate with known virulence factors. However, a close correlation (r = 0.97) existed between ciliary slowing and pigment content. In a prolonged culture, the increase in activity correlated (r = 0.94) with pigment accumulation. Gel filtration of lyophilized filtrate yielded a single peak of activity corresponding to the pigment fraction. Pyocyanin extracted from an active strain, and 1-hydroxyphenazine were purified by high performance liquid chromatography, and characterized by ultraviolet absorbance spectra and mass spectrometry. Both slowed cilia in a dose-dependent manner, and were synthesized and shown to be indistinguishable from the biological compounds. Pyocyanin caused gradual onset of slowing and ultimate widespread ciliostasis with epithelial disruption. 1-hydroxyphenazine caused rapid onset of ciliary slowing associated with dyskinesia and ciliostasis. Pyocyanin assayed within filtrates accounted for a significant proportion of the bioactivity present.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / pharmacology
  • Cilia / drug effects*
  • Epithelium / drug effects
  • Humans
  • In Vitro Techniques
  • Lipopolysaccharides / pharmacology
  • Phenazines / isolation & purification
  • Phenazines / pharmacology*
  • Pigments, Biological / analysis
  • Pseudomonas aeruginosa / pathogenicity*
  • Pyocyanine / isolation & purification
  • Pyocyanine / pharmacology*
  • Respiratory System / drug effects*

Substances

  • Alginates
  • Lipopolysaccharides
  • Phenazines
  • Pigments, Biological
  • 1-hydroxyphenazine
  • Pyocyanine