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Instability of in vitro resistance to imipenem in Pseudomonas aeruginosa
1Institute of Experimental Epidemiology, Wernigerode.
Abstract:
In 3 from 19 clinical isolates of Pseudomonas aeruginosa imipenem-resistant subpopulations could be detected in vitro. In comparison to their wild strains these imipenem-resistant cells were lacking an outer-membrane-protein of 50 kD. In the subpopulation derived from Pseudomonas aeruginosa 76 resistance to imipenem was found to be instable. It could be lost within a short period of time after subcultivation in the absence of imipenem. Cells with restored sensitivity to imipenem possess the outer membrane protein of 50 kD as the wild strain does.
Insights
Imipenem resistance in Pseudomonas aeruginosa can emerge from subpopulations lacking a 50 kD outer membrane protein. This resistance is often unstable and can be regained by restoring the protein.
Area of Science:
- Microbiology
- Bacterial genetics
- Antibiotic resistance
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen known for its intrinsic and acquired resistance to antibiotics.
- Carbapenem antibiotics, such as imipenem, are crucial for treating multidrug-resistant bacterial infections.
- Mechanisms of antibiotic resistance in P. aeruginosa are diverse and can involve alterations in outer membrane proteins.
Purpose of the Study:
- To investigate the emergence and characteristics of imipenem-resistant subpopulations in clinical isolates of Pseudomonas aeruginosa.
- To identify potential molecular mechanisms associated with imipenem resistance in these subpopulations.
Main Methods:
- In vitro culture of clinical isolates of Pseudomonas aeruginosa.
- Detection and isolation of imipenem-resistant subpopulations.
- Comparison of outer membrane protein profiles between wild-type and resistant strains using techniques like SDS-PAGE.
- Assessment of resistance stability through subcultivation in the absence of imipenem.
Main Results:
- Imipenem-resistant subpopulations were detected in vitro in 3 out of 19 clinical isolates of P. aeruginosa.
- These resistant subpopulations consistently lacked an outer membrane protein of approximately 50 kD compared to their susceptible wild-type strains.
- For one isolate (P. aeruginosa 76), imipenem resistance was found to be unstable, being lost upon subcultivation without the antibiotic.
- Restored susceptibility in these subpopulations correlated with the re-expression of the 50 kD outer membrane protein.
Conclusions:
- The absence of a specific 50 kD outer membrane protein is strongly associated with in vitro imipenem resistance in certain P. aeruginosa clinical isolates.
- Imipenem resistance mediated by this mechanism can be unstable and reversible, suggesting potential therapeutic strategies.
- Further research into the function of this 50 kD protein could elucidate novel targets for combating P. aeruginosa infections.