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Outer membrane permeability of Serratia marcescens to meropenem and imipenem
A Raimondi1, A Pessina, G Cocuzza
1Institute of Medical Microbiology, University of Milan, Italy.
Abstract:
The penetration rates of meropenem and imipenem through the outer membrane (OM) of Serratia marcescens was evaluated by the method of Zimmermann and Rosselet. To this aim, two strains of the specie were transformed with the pMON-01 plasmid DNA that carries the bla S gene from Xanthomonas maltophilia encoding for the L-1 beta-lactamase. The permeability of the transformants to cephaloridine was not affected by the presence of the plasmid. Imipenem was shown to penetrate the OM of the transformants at a rate 4- to 5-fold higher than that of meropenem and close to that of cephaloridine. Meropenem appeared more active than imipenem in inhibiting the targets as inferred from the calculated concentrations of antibiotic in the cell periplasm in the presence of MIC. The calculation of the target access index (TAI) indicated that a 20- to 50-fold decrease in permeability or increase in beta-lactamase activity would be required to significantly increase the MICs of imipenem or meropenem for these strains.
Insights
Imipenem penetrates Serratia marcescens outer membrane faster than meropenem. However, meropenem is more effective at inhibiting bacterial targets, suggesting improved therapeutic potential despite lower penetration rates.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Serratia marcescens is an opportunistic pathogen.
- Carbapenem antibiotics like meropenem and imipenem are crucial for treating infections caused by Gram-negative bacteria.
- Outer membrane (OM) penetration is a key factor determining antibiotic efficacy against Gram-negative bacteria.
Purpose of the Study:
- To compare the outer membrane penetration rates of meropenem and imipenem in Serratia marcescens.
- To evaluate the impact of L-1 beta-lactamase expression on carbapenem efficacy.
- To assess the potential of meropenem and imipenem for treating Serratia marcescens infections.
Main Methods:
- Zimmermann and Rosselet method for evaluating antibiotic penetration.
- Transformation of Serratia marcescens with pMON-01 plasmid carrying the L-1 beta-lactamase gene (bla S).
- Measurement of cephaloridine permeability in transformants.
- Calculation of antibiotic concentrations in the periplasm and Target Access Index (TAI).
Main Results:
- Imipenem penetrated the OM of transformants 4- to 5-fold higher than meropenem.
- Meropenem demonstrated higher activity in inhibiting bacterial targets, despite lower OM penetration.
- A significant increase in minimum inhibitory concentrations (MICs) would require substantial changes in OM permeability or beta-lactamase activity.
Conclusions:
- Imipenem exhibits superior outer membrane permeability in Serratia marcescens compared to meropenem.
- Meropenem shows greater intracellular activity, suggesting it may be more effective therapeutically.
- Modifications in outer membrane permeability or beta-lactamase expression are critical determinants of carbapenem resistance.