Detection of Pseudomonas aeruginosa cell-to-cell signals in lung tissue of cystic fibrosis patients

Chronic Pseudomonas aeruginosa infections lead to progressive lung tissue destruction in cystic fibrosis (CF) patients. Two bacterial cell-to-cell signals, 3-oxo-C-12-HSL and C-4-HSL are required for the production of several extracellular virulence factors. 3-oxo-C-12-HSL is also required for the development of a differentiated biofilm, induces IL-8 production by epithelial cells and possesses immunomodulatory activities. These two signalling molecules are therefore believed to play a role in the pathogenesis of R aeruginosa infections, but have never been isolated from infected human tissues. We extracted and quantified the two P. aeruginosa cell-to-cell signals from lung tissues of two CF patients infected by P aeruginosa. 3-oxo-C-12-HSL and C-4-HSL were detected in the lung tissues in fmol/gram, respectively pmol/gram concentrations; the ratio C-4-HSL/3-oxo-C-12-HSL exceeded 100 in all tissue samples. Random Amplified Polymorphism DNA genotyping revealed that one genotype was present per lung. In vitro the P aeruginosa isolates from the two lungs produced 3-oxo-C-12-HSL, whereas some isolates did not produce detectable C-4-HSL. Our results suggest that both R aeruginosa cell-to-cell signals were produced in the lung tissue of these two cystic fibrosis patients. (C) 2002 Elsevier Science Ltd.