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Outer membrane permeability and beta-lactamase content in Pseudomonas maltophilia clinical isolates and laboratory
1Pharmaceuticals Division, CIBA-GEIGY Limited, Basel, Switzerland.
Abstract:
Low outer-membrane permeability appears to be responsible for the generally high degree of antibiotic resistance of Pseudomonas maltophilia. Constitutive overproduction of beta-lactamases affects the sensitivity of these bacteria only to those beta-lactam antibiotics that are hydrolyzed by strain-specific beta-lactamases and that do not efficiently induce these enzymes in inducible strains.
Insights
Pseudomonas maltophilia exhibits high antibiotic resistance due to low outer-membrane permeability. Beta-lactamase overproduction impacts sensitivity to specific beta-lactam antibiotics, depending on enzyme activity and induction.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Pseudomonas maltophilia is a significant opportunistic pathogen.
- High levels of antibiotic resistance are frequently observed in clinical isolates.
- Understanding resistance mechanisms is crucial for effective treatment strategies.
Purpose of the Study:
- To investigate the primary mechanisms contributing to the antibiotic resistance of Pseudomonas maltophilia.
- To elucidate the role of outer-membrane permeability and beta-lactamase activity in Pseudomonas maltophilia's resistance profile.
Main Methods:
- Analysis of outer-membrane protein expression and composition.
- Determination of minimum inhibitory concentrations (MICs) for various antibiotics.
- Enzymatic assays to quantify beta-lactamase activity.
- Assessment of beta-lactamase induction by different beta-lactam antibiotics.
Main Results:
- Reduced outer-membrane permeability was identified as a key factor in the overall antibiotic resistance of Pseudomonas maltophilia.
- Constitutive overproduction of beta-lactamases contributes to resistance against specific beta-lactam antibiotics.
- The sensitivity to beta-lactam antibiotics is influenced by the specific beta-lactamases produced by the strain and their inducibility.
Conclusions:
- Low outer-membrane permeability is a major determinant of antibiotic resistance in Pseudomonas maltophilia.
- Beta-lactamase activity plays a strain-specific role in resistance, particularly against certain beta-lactam agents.
- Targeting outer-membrane function and understanding beta-lactamase dynamics are potential strategies for combating Pseudomonas maltophilia infections.