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Effects of antibiotics on quorum sensing in Pseudomonas aeruginosa
Mette E Skindersoe1, Morten Alhede, Richard Phipps
1Biomedical Microbiology, BioSys, Technical University of Denmark, Kgs. Lyngby DK-2800, Denmark.
Abstract:
During infection, Pseudomonas aeruginosa employs bacterial communication (quorum sensing [QS]) to coordinate the expression of tissue-damaging factors. QS-controlled gene expression plays a pivotal role in the virulence of P. aeruginosa, and QS-deficient mutants cause less severe infections in animal infection models. Treatment of cystic fibrosis (CF) patients chronically infected with P. aeruginosa with the macrolide antibiotic azithromycin (AZM) has been demonstrated to improve the clinical outcome. Several studies indicate that AZM may accomplish its beneficial action in CF patients by impeding QS, thereby reducing the pathogenicity of P. aeruginosa. This led us to investigate whether QS inhibition is a common feature of antibiotics. We present the results of a screening of 12 antibiotics for their QS-inhibitory activities using a previously described QS inhibitor selector 1 strain. Three of the antibiotics tested, AZM, ceftazidime (CFT), and ciprofloxacin (CPR), were very active in the assay and were further examined for their effects on QS-regulated virulence factor production in P. aeruginosa. The effects of the three antibiotics administered at subinhibitory concentrations were investigated by use of DNA microarrays. Consistent results from the virulence factor assays, reverse transcription-PCR, and the DNA microarrays support the finding that AZM, CFT, and CPR decrease the expression of a range of QS-regulated virulence factors. The data suggest that the underlying mechanism may be mediated by changes in membrane permeability, thereby influencing the flux of N-3-oxo-dodecanoyl-L-homoserine lactone.
Insights
Certain antibiotics, including azithromycin, ceftazidime, and ciprofloxacin, can inhibit Pseudomonas aeruginosa quorum sensing (QS). This QS inhibition reduces the expression of virulence factors, offering a potential new strategy for treating infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Pseudomonas aeruginosa uses quorum sensing (QS) to regulate virulence factors, crucial for infection severity.
- Antibiotic treatment, like azithromycin for cystic fibrosis patients, may work by disrupting QS.
Purpose of the Study:
- To investigate if QS inhibition is a common antibiotic mechanism.
- To screen antibiotics for QS inhibitory activity and assess their impact on P. aeruginosa virulence.
Main Methods:
- Screened 12 antibiotics for QS inhibitory activity using a specific bacterial strain.
- Examined the effects of azithromycin, ceftazidime, and ciprofloxacin on QS-regulated virulence factors at subinhibitory concentrations.
- Utilized DNA microarrays, virulence factor assays, and reverse transcription-PCR to analyze gene expression.
Main Results:
- Azithromycin, ceftazidime, and ciprofloxacin demonstrated significant QS inhibitory activity.
- These antibiotics decreased the expression of multiple QS-regulated virulence factors in P. aeruginosa.
- The mechanism may involve altered membrane permeability affecting QS signal molecules.
Conclusions:
- QS inhibition is a potential mechanism of action for certain antibiotics against P. aeruginosa.
- Azithromycin, ceftazidime, and ciprofloxacin can reduce P. aeruginosa pathogenicity by interfering with QS.
- This finding suggests a novel therapeutic approach for P. aeruginosa infections.
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