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

• Published in: The Journal of clinical investigation Vol. 79; no. 1; pp. 221 - 229
• Main Authors: WILSON, R, PITT, T, TAYLOR, G, WATSON, D, MACDERMOT, J, SYKES, D, ROBERTS, D, COLE, P
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 1987
• Subjects: Alginates - pharmacology; Applied sciences; Biological and medical sciences; Cilia - drug effects; Epithelium - drug effects; Exact sciences and technology; Humans; In Vitro Techniques; Lipopolysaccharides - pharmacology; Medical sciences; Other techniques and industries; Pharmacology. Drug treatments; Phenazines - isolation & purification; Phenazines - pharmacology; Pigments, Biological - analysis; Pseudomonas aeruginosa; Pseudomonas aeruginosa - pathogenicity; Pyocyanine - isolation & purification; Pyocyanine - pharmacology; Respiratory system; Respiratory System - drug effects; Ciliated cell; Motility; Inhibition; Respiratory epithelium; Biological activity
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI112787

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.