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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References
Costerton, J. W., Stewart, P. S. & Greenberg, E. P. Bacterial biofilms: a common cause of persistant infections. Science 284, 1318– 1322 (1999).
Burns, J. L., Ramsey, B. W. & Smith, A. L. Clinical manifestations and treatment of pulmonary infections in cystic fibrosis. Adv. Pediatr. Infect. Dis. 8, 53–66 (1993).
Hoiby, N. Antibiotic therapy for chronic infection of Pseudomonas in the lung. Annu. Rev. Med. 44, 1– 10 (1993).
Costerton, J. W., Lewandowski, Z., Caldwell, D. E., Korber, D. R. & Lappin-Scott, H. M. Microbial biofilms. Annu. Rev. Microbiol. 49, 711–745 (1995).
Davies, D. G. et al. The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 280, 295 –298 (1998).
Welsh, M. J., Tsui, L.-C., Boat, T. F. & Beaudet, A. L. in Metabolic and Molecular Basis of Inherited Diseases Vol. III (eds Scriver, C. R., Beaudet, A. L., Sly, W. S. & Valle, D.) 3799– 3876 (McGraw-Hill, New York, 1995).
Mendelman, P. et al. Aminoglycoside penetration, inactivation, and efficacy in cystic fibrosis sputum. Am. Rev. Respir. Dis. 132, 761–765 (1985).
Whiteley, M., Lee, K. M. & Greenberg, E. P. Identification of genes controlled by quorum sensing in Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA 96, 13904–13909 (1999).
Pesci, E. C. & Iglewski, B. H. The chain of command in Pseudomonas quorum sensing. Trends Microbiol. 5 , 132–135 (1997).
Tang, H. B. et al. Contribution of specific Pseudomonas aeruginosa virulence factors to pathogenesis of pneumonia in a neonatal mouse model of infection. Infect. Immun. 64, 37– 43 (1996).
Rumbaugh, K. P., Griswold, J. A. & Hamood, A. N. Contribution of the regulatory gene lasR to the pathogenesis of Pseudomonas aeruginosa infection of burned mice. J. Burn Care Rehabil. 20, 42– 49 (1999).
Schaefer, A. L., Hanzelka, B. L., Parsek, M. R. & Greenberg, E. P. Detection, purification and structural elucidation of acylhomoserine lactone inducer of Vibrio fischeri luminescence and other related molecules. Methods Enzymol. 305, 288– 301 (2000).
Schaefer, A. L., Greenberg, E. P. & Parsek, M. R. Methods Enzymol. (in the press).
Costerton, J. W. The etiology and persistence of cryptic bacterial infections: a hypothesis. Rev. Infect. Dis. 6, S608– S616 (1984).
Costerton, J. W., Lam, J., Lam, K. & Chan, R. The role of the microcolony mode of growth in the pathogenesis of Pseudomonas aeruginosa infections. Rev. Infect. Dis. 5, S867– S873 (1983).
Pearson, J. P. et al. Structure of the autoinducer required for expression of Pseudomonas aeruginosa virulence genes. Proc. Natl Acad. Sci. USA 91, 197–201 ( 1994).
Jensen, J. E., Fecycz, T. & Campell, J. N. Nutritional factors controlling exocellular protease production by Pseudomonas aeruginosa. J. Bacteriol. 144, 844–847 (1980).
Davies, D. G., Chakrabarty, A. M. & Geesey, G. G. Exopolysaccharide production in biofilms: substratum activation of alginate gene expression by Pseudomonas aeruginosa. Applied Environ. Microbiol. 59, 1181– 1186 (1993).
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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DOI: https://doi.org/10.1038/35037627
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