Related Experiment Videos
Imipenem resistance in Pseudomonas aeruginosa resulting from diminished expression of an outer membrane protein
Abstract:
The mechanism of Pseudomonas aeruginosa resistance to imipenem in five imipenem-susceptible clinical isolates and in their resistant counterparts was investigated. The frequency for selecting imipenem-resistant variants ranged from 2.7 X 10(-5) to 2.1 X 10(-8) and was comparable to those for other beta-lactams. Cross-resistance between imipenem and other beta-lactam compounds was not observed. In all imipenem-resistant variants, induction of chromosomal beta-lactamase by imipenem was markedly diminished compared with that in the susceptible parent strain. This was not the case for other inducers such as ampicillin or cefoxitin, suggesting an impaired uptake of imipenem as an explanation for resistance. Analysis of the outer membrane proteins revealed a marked decrease of either a 46- or a 45-kilodalton protein. The lipopolysaccharide of the outer membrane in the imipenem-resistant variants was not altered.
Insights
Pseudomonas aeruginosa resistance to imipenem may stem from impaired drug uptake, not altered beta-lactamase induction. Outer membrane protein changes, not lipopolysaccharide alterations, are linked to this imipenem resistance.
Area of Science:
- Microbiology
- Molecular Biology
- Drug Resistance
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen known for developing antibiotic resistance.
- Carbapenem antibiotics, like imipenem, are crucial for treating serious infections caused by multidrug-resistant bacteria.
- Understanding the mechanisms of resistance is vital for effective antimicrobial stewardship.
Purpose of the Study:
- To investigate the mechanisms underlying imipenem resistance in clinical isolates of Pseudomonas aeruginosa.
- To compare imipenem-susceptible strains with their resistant counterparts to identify key differences.
Main Methods:
- Induction of chromosomal beta-lactamase by imipenem, ampicillin, and cefoxitin was assessed.
- Outer membrane proteins and lipopolysaccharides were analyzed in susceptible and resistant strains.
- Frequency of imipenem-resistant variant selection was determined.
Main Results:
- Imipenem resistance occurred at frequencies comparable to other beta-lactams, without cross-resistance.
- Induction of chromosomal beta-lactamase by imipenem was significantly reduced in resistant variants.
- A marked decrease in a 46- or 45-kilodalton outer membrane protein was observed in resistant strains.
- Lipopolysaccharide composition remained unchanged in imipenem-resistant variants.
Conclusions:
- Impaired uptake of imipenem, potentially due to alterations in specific outer membrane proteins, is a likely mechanism for resistance in Pseudomonas aeruginosa.
- Reduced beta-lactamase induction by imipenem in resistant strains suggests a primary role for uptake rather than enzymatic degradation.
- These findings highlight the importance of outer membrane permeability in carbapenem resistance.