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Imipenem resistance in Acinetobacter baumanii is due to altered penicillin-binding proteins
M Gehrlein1, H Leying, W Cullmann
1Abteilung Medizinische Mikrobiologie und Immunologie, Ruhr-Universität Bochum, BRD.
Abstract:
The comparison of a clinical Acinetobacter baumanii isolate (strain No. 4852/88) and its selected imipenem-resistant (IMR) clone exhibited a complex reorganization of the penicillin-binding proteins (PBPs) with diminished labelling of all PBPs except the 24-kD PBP which showed an increased binding of 14C-penicillin. This protein could not be saturated by preincubation of membranes with imipenem at 8-fold the MIC of imipenem, thus indicating PBP alterations responsible for imipenem resistance. In A. baumanii 4852/88 seven PBPs with the apparent molecular weights of 94, 84, 65, 61, 48, 40 and 24 kD could be detected. beta-Lactamase production was barely detectable in any case and could not be enhanced in the presence of various beta-lactams as the inducer. The outer membrane proteins were found identical in both the wild-type strain and the Im clone. So far, imipenem-resistant A. baumanii isolates have been isolated twice in our diagnostic laboratory; however, no implications on the future relevance of the above findings can be made.
Insights
Imipenem resistance in Acinetobacter baumanii involves altered penicillin-binding proteins (PBPs). A specific 24-kD PBP showed increased binding, indicating a key mechanism for resistance in this bacterium.
Area of Science:
- Microbiology
- Molecular Biology
- Drug Resistance
Background:
- Acinetobacter baumanii is an opportunistic pathogen known for its resistance to antibiotics.
- Imipenem is a critical carbapenem antibiotic used to treat severe infections.
Purpose of the Study:
- To investigate the molecular mechanisms underlying imipenem resistance in a clinical isolate of Acinetobacter baumanii.
- To compare the penicillin-binding protein (PBP) profiles of a wild-type strain and its imipenem-resistant (IMR) clone.
Main Methods:
- Comparative analysis of penicillin-binding proteins (PBPs) using 14C-penicillin labeling.
- Detection and characterization of outer membrane proteins.
- Assessment of beta-lactamase production.
Main Results:
- A complex reorganization of PBPs was observed in the IMR clone.
- Diminished labeling of most PBPs, except for a 24-kD PBP with increased 14C-penicillin binding.
- The 24-kD PBP could not be saturated by imipenem, suggesting PBP alterations as the cause of resistance.
- Beta-lactamase production was minimal and not inducible.
- Outer membrane protein profiles were identical between wild-type and IMR strains.
Conclusions:
- Alterations in penicillin-binding proteins, particularly the 24-kD PBP, are a key mechanism for imipenem resistance in this Acinetobacter baumanii isolate.
- The findings provide insight into the molecular basis of carbapenem resistance in A. baumanii.
- Further surveillance is needed to determine the clinical relevance of these resistance mechanisms.