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Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms
P K Singh1, A L Schaefer, M R Parsek
1Howard Hughes Medical Institute & Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Abstract:
The bacterium Pseudomonas aeruginosa permanently colonizes cystic fibrosis lungs despite aggressive antibiotic treatment. This suggests that P. aeruginosa might exist as biofilms--structured communities of bacteria encased in a self-produced polymeric matrix--in the cystic fibrosis lung. 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 formation. 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.
Insights
Pseudomonas aeruginosa forms biofilms in cystic fibrosis lungs, coordinating via quorum-sensing signals. Signal profiling may identify new anti-biofilm agents for cystic fibrosis treatment.
Area of Science:
- Microbiology
- Medical Science
- Biochemistry
Background:
- Pseudomonas aeruginosa frequently colonizes cystic fibrosis lungs despite antibiotic treatment.
- This suggests the bacterium may form biofilms—structured, matrix-encased communities—within the lungs.
- Microscopy of cystic fibrosis sputum confirms P. aeruginosa in biofilm-like structures.
Purpose of the Study:
- To investigate the role of quorum-sensing signals in P. aeruginosa biofilm formation within cystic fibrosis sputum.
- To analyze the relative abundance of quorum-sensing signals in cystic fibrosis sputum compared to laboratory conditions.
- To assess the potential of quorum-sensing signal profiling as a biomarker for identifying anti-biofilm agents.
Main Methods:
- Microscopic analysis of cystic fibrosis sputum to identify bacterial structures.
- Quantification of two principal P. aeruginosa quorum-sensing signals in sputum and laboratory cultures.
- Cultivation of P. aeruginosa isolates from sputum and the standard strain PAO1 in broth and a laboratory biofilm model.
Main Results:
- Cystic fibrosis sputum contains the two main P. aeruginosa quorum-sensing signals, but in reversed relative abundance compared to standard laboratory cultures.
- Some P. aeruginosa sputum isolates exhibited standard signal ratios in broth, but shifted to sputum-like ratios in a laboratory biofilm model.
- Laboratory biofilm models replicated the reversed signal ratios observed in cystic fibrosis sputum.
Conclusions:
- The findings support the hypothesis that P. aeruginosa exists as biofilms in cystic fibrosis sputum.
- Quorum-sensing signal profiling of P. aeruginosa strains shows promise as a biomarker.
- This profiling could aid in screening for novel agents that disrupt P. aeruginosa biofilm development.
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