Pyocyanin and 1-hydroxyphenazine produced by Pseudomonas aeruginosa inhibit the beating of human respiratory cilia in vitro.
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.
D000464:Alginates / Q000494:pharmacology; D002923:Cilia / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D010619:Phenazines / Q000302:isolation & purification / Q000494:pharmacology*; D010860:Pigments, Biological / Q000032:analysis; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D011710:Pyocyanine / Q000302:isolation & purification / Q000494:pharmacology*; D012137:Respiratory System / Q000187:drug effects*
D000464:Alginates; D008070:Lipopolysaccharides; D010619:Phenazines; D010860:Pigments, Biological; C050093:1-hydroxyphenazine; D011710:Pyocyanine