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Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms

Abstract

The bacterium Pseudomonas aeruginosa permanently colonizes cystic fibrosis lungs despite aggressive antibiotic treatment1,2,3. This suggests that P. aeruginosa might exist as biofilms—structured communities of bacteria encased in a self-produced polymeric matrix—in the cystic fibrosis lung1,4. Consistent with this hypothesis, microscopy of cystic fibrosis sputum shows that P. aeruginosa are in biofilm-like structures. P. aeruginosa uses extracellular quorum-sensing signals (extracellular chemical signals that cue cell-density-dependent gene expression) to coordinate biofilm formation5. Here we found that cystic fibrosis sputum produces the two principal P. aeruginosa quorum-sensing signals; however, the relative abundance of these signals was opposite to that of the standard P. aeruginosa strain PAO1 in laboratory broth culture. When P. aeruginosa sputum isolates were grown in broth, some showed quorum-sensing signal ratios like those of the laboratory strain. When we grew these isolates and PAO1 in a laboratory biofilm model, the signal ratios were like those in cystic fibrosis sputum. Our data support the hypothesis that P. aeruginosa are in a biofilm in cystic fibrosis sputum. Moreover, quorum-sensing signal profiling of specific P. aeruginosa strains may serve as a biomarker in screens to identify agents that interfere with biofilm development.

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Figure 1: Transmission electron microscope images of P. aeruginosa in sputum.
Figure 2: Acyl-HSL profiles of P. aeruginosa broth cultures and CF sputum samples.
Figure 3: Comparisons of acyl-HSL ratios in biofilms with those in broth cultures.

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Acknowledgements

We thank J. Launspach, C. Clark, and the University of Iowa Clinical Microbiology Laboratory for providing the data in Table 1. Funding was provided by the National Insititute of General Medical Sciences, the National Heart, Lung, and Blood Institute, and the Cystic Fibrosis Foundation. A.L.S. was a NIH Graduate Trainee, M.R.P. was the recipient of an NIH Postdoctoral Research Service Award, and P.K.S. is the recipient of an NIH Mentored Physician Scientist Award and a Cystic Fibrosis Foundation Leroy Matthews Award.

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Singh, P., Schaefer, A., Parsek, M. et al. Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407, 762–764 (2000). https://doi.org/10.1038/35037627

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