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Published on: January 1, 2016
Anionic fluoroquinolones as antibacterials against biofilm-producing Pseudomonas aeruginosa
Timothy E Long1, Lexie C Keding2, Demetria D Lewis3
1Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV 25755, United States; Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
Abstract:
Pseudomonas aeruginosa is a common biofilm-forming bacterial pathogen implicated in diseases of the lungs. The extracellular polymeric substances (EPS) of respiratory Pseudomonas biofilms are largely comprised of anionic molecules such as rhamnolipids and alginate that promote a mucoid phenotype. In this Letter, we examine the ability of negatively-charged fluoroquinolones to transverse the EPS and inhibit the growth of mucoid P. aeruginosa. Anionic fluoroquinolones were further compared with standard antibiotics via a novel microdiffusion assay to evaluate drug penetration through pseudomonal alginate and respiratory mucus from a patient with cystic fibrosis.
Insights
Negatively-charged fluoroquinolones show potential for penetrating Pseudomonas aeruginosa biofilms and inhibiting bacterial growth. This study compared their efficacy against standard antibiotics in cystic fibrosis mucus.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Pseudomonas aeruginosa is a significant bacterial pathogen forming biofilms, particularly in lung infections.
- Respiratory Pseudomonas biofilms contain anionic extracellular polymeric substances (EPS), like alginate and rhamnolipids, contributing to a mucoid phenotype.
Purpose of the Study:
- To investigate the efficacy of anionic fluoroquinolones in penetrating Pseudomonas aeruginosa EPS.
- To assess the growth inhibition of mucoid P. aeruginosa by anionic fluoroquinolones.
- To compare the drug penetration of anionic fluoroquinolones with standard antibiotics.
Main Methods:
- Utilized a novel microdiffusion assay.
- Evaluated drug penetration through purified pseudomonal alginate.
- Assessed drug penetration through respiratory mucus from cystic fibrosis patients.
Main Results:
- Anionic fluoroquinolones demonstrated the ability to traverse the EPS layer of Pseudomonas biofilms.
- The study provided comparative data on the penetration of anionic fluoroquinolones versus standard antibiotics.
- Efficacy was tested in relevant models including patient-derived cystic fibrosis mucus.
Conclusions:
- Anionic fluoroquinolones represent a promising therapeutic strategy for combating Pseudomonas aeruginosa biofilm infections.
- The findings suggest potential for improved antibiotic delivery across challenging biofilm structures in respiratory diseases.
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