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Membrane permeability of Pseudomonas aeruginosa to 4-quinolones
P Kubesch1, M Wehsling, B Tümmler
1Zentrum Biochemie II, Medizinische Hochschule Hannover, Federal Republic of Germany.
Abstract:
The outer membrane-disorganizing agent polymyxin B nonapeptide sensitized Pseudomonas aeruginosa strains 2-40fold to ciprofloxacin, norfloxacin, and ofloxacin, and 80-200fold to nalidixic acid. Sensitized P. aeruginosa strains were nearly as susceptible to nalidixic acid as Escherichia coli strains. The data suggest that the outer membrane permeability is of critical importance for the antipseudomonal activity of 4-quinolones. The low penetration of the outer membrane is the major cause of the nalidixic acid resistance of P. aeruginosa.
Insights
Polymyxin B nonapeptide significantly increased Pseudomonas aeruginosa susceptibility to fluoroquinolones and nalidixic acid. This highlights the outer membrane
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen known for its intrinsic resistance to many antibiotics.
- The outer membrane of Gram-negative bacteria, including P. aeruginosa, acts as a significant barrier to drug penetration.
- 4-quinolones are a class of antibiotics widely used to treat bacterial infections.
Purpose of the Study:
- To investigate the effect of polymyxin B nonapeptide on the susceptibility of Pseudomonas aeruginosa to various 4-quinolone antibiotics.
- To elucidate the role of outer membrane permeability in the resistance mechanisms of P. aeruginosa against 4-quinolones.
Main Methods:
- Treatment of Pseudomonas aeruginosa strains with polymyxin B nonapeptide, an outer membrane-disrupting agent.
- Assessment of bacterial susceptibility to ciprofloxacin, norfloxacin, ofloxacin, and nalidixic acid using standard microbiological assays.
- Comparative analysis of antibiotic susceptibility between sensitized P. aeruginosa strains and susceptible Escherichia coli strains.
Main Results:
- Polymyxin B nonapeptide treatment sensitized P. aeruginosa strains 2-40 fold to ciprofloxacin, norfloxacin, and ofloxacin.
- A more pronounced sensitization, 80-200 fold, was observed for nalidixic acid.
- Sensitized P. aeruginosa strains exhibited susceptibility to nalidixic acid comparable to that of Escherichia coli strains.
Conclusions:
- Outer membrane permeability is a critical factor determining the efficacy of 4-quinolones against Pseudomonas aeruginosa.
- Reduced penetration through the outer membrane is the primary reason for nalidixic acid resistance in P. aeruginosa.
- Targeting outer membrane permeability could be a viable strategy to overcome antibiotic resistance in P. aeruginosa infections.