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Imipenem: morphological changes and lethal effects on Pseudomonas aeruginosa
N A Carlone1, M Ferrero, A M Cuffini
1Institute of Microbiology, University of Turin, Italy.
Abstract:
Imipenem, a new carbapenem antibiotic shows an extremely broad spectrum of antibacterial activity for almost all Gram-negative and Gram-positive aerobic and anaerobic bacteria. It is stable to beta-lactamases and shows a high affinity for PBP 2. The changes in morphology and ultrastructure caused by the antibiotic on Ps. aeruginosa confirm that imipenem acts by binding primarily to PBP 2, resulting in irregular and round shaped cells, and later during treatment to PBP 1 with cellular lysis. The involvement of PBP 1 is also demonstrated by the fast bactericidal kinetics on Ps. aeruginosa, E. coli and Staph. aureus.
Insights
Imipenem, a novel carbapenem antibiotic, exhibits broad-spectrum antibacterial activity and stability against beta-lactamases. It targets penicillin-binding proteins (PBPs), primarily PBP 2, leading to bacterial cell shape changes and lysis.
Area of Science:
- Microbiology
- Pharmacology
- Bacteriology
Background:
- Imipenem is a novel carbapenem antibiotic.
- It demonstrates broad-spectrum activity against Gram-negative and Gram-positive bacteria, including aerobes and anaerobes.
- Imipenem is stable in the presence of beta-lactamases.
Purpose of the Study:
- To investigate the mechanism of action of imipenem.
- To determine the primary bacterial targets of imipenem.
- To elucidate the morphological and ultrastructural changes induced by imipenem in bacteria.
Main Methods:
- Antibacterial activity spectrum analysis.
- Penicillin-binding protein (PBP) affinity studies.
- Microscopic examination of bacterial morphology and ultrastructure (e.g., on Pseudomonas aeruginosa).
- Assessment of bactericidal kinetics.
Main Results:
- Imipenem exhibits high affinity for PBP 2.
- Morphological changes in Pseudomonas aeruginosa include irregular and round cell shapes.
- Later-stage treatment involves PBP 1, leading to cellular lysis.
- Rapid bactericidal effects were observed against Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus.
Conclusions:
- Imipenem's primary target is PBP 2, causing initial morphological alterations.
- Involvement of PBP 1 contributes to imipenem's potent bactericidal activity and cell lysis.
- Imipenem represents a significant advancement in broad-spectrum antibiotic therapy.