Loss of a 29-kilodalton outer membrane protein in Acinetobacter baumannii is associated with imipenem resistance
Adriana S Limansky1, María Alejandra Mussi, Alejandro M Viale
1Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, 2000 Rosario, Argentina.
Abstract:
We analyzed the possible causes of imipenem (IPM) resistance in multidrug-resistant isolates of Acinetobacter baumannii. Comparison of the outer membrane protein (OMP) profiles of two genomically related strains (Ab288 [IPM sensitive] and Ab242 [IPM resistant]) indicated the conspicuous loss of a 29-kDa polypeptide in the Ab242 strain. No carbapenemase activity was detected in any of these strains. The treatment of Ab288 with sodium salicylate resulted in IPM resistance and the loss of the 29-kDa OMP. In addition, IPM-resistant clones of Ab288 which were selected by repetitive culturing in increasing concentrations of this antibiotic also showed the absence of this 29-kDa OMP.
Insights
Acinetobacter baumannii resistance to imipenem (IPM) is linked to the loss of a specific 29-kDa outer membrane protein (OMP). This OMP loss occurs with IPM exposure and sodium salicylate treatment, suggesting its role in IPM resistance.
Area of Science:
- Microbiology
- Molecular Biology
- Antimicrobial Resistance
Background:
- Acinetobacter baumannii is a significant multidrug-resistant pathogen.
- Carbapenem resistance is a growing concern in A. baumannii infections.
- Mechanisms of imipenem resistance in A. baumannii are not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms underlying imipenem (IPM) resistance in multidrug-resistant Acinetobacter baumannii.
- To identify potential outer membrane protein (OMP) alterations associated with IPM resistance.
Main Methods:
- Comparative analysis of outer membrane protein (OMP) profiles between imipenem-sensitive and imipenem-resistant strains.
- Genomic comparison of related strains to identify genetic differences.
- Induction of imipenem resistance through chemical treatment (sodium salicylate) and antibiotic selection.
- Detection of carbapenemase activity.
Main Results:
- A conspicuous loss of a 29-kDa outer membrane protein (OMP) was observed in an imipenem-resistant Acinetobacter baumannii strain (Ab242) compared to a sensitive strain (Ab288).
- No carbapenemase activity was detected in the analyzed strains.
- Treatment of the sensitive strain with sodium salicylate induced imipenem resistance and resulted in the loss of the 29-kDa OMP.
- Imipenem-resistant clones selected through serial subculturing also exhibited the absence of this 29-kDa OMP.
Conclusions:
- The loss of a specific 29-kDa outer membrane protein (OMP) is strongly associated with imipenem resistance in Acinetobacter baumannii.
- This OMP appears to play a crucial role in maintaining susceptibility to imipenem.
- Mechanisms other than carbapenemase production are involved in imipenem resistance in these isolates.
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