Imipenem resistance associated with the loss of a 40 kDa outer membrane protein in Enterobacter aerogenes

Area of Science:

• Microbiology
• Bacterial Physiology

Background:

• Enterobacter aerogenes is an opportunistic pathogen.
• Antibiotic resistance, particularly to carbapenems like imipenem, is a growing public health concern.
• Outer membrane proteins (OMPs) play a vital role in bacterial cell structure and function, including antibiotic permeability.

Purpose of the Study:

• To investigate the role of outer membrane proteins (OMPs) in the imipenem resistance of Enterobacter aerogenes.
• To characterize the OMP profile of an imipenem-resistant strain (EA-Z) and compare it to susceptible strains and mutants.

Main Methods:

• Isolation and characterization of an imipenem-resistant Enterobacter aerogenes strain (EA-Z) from a blood culture.
• Analysis of Outer Membrane Protein (OMP) profiles using gel electrophoresis.
• Comparison of OMP profiles between resistant and susceptible strains, as well as laboratory-selected mutants.
• Detection of beta-lactamase activity and assessment of imipenem hydrolysis.

Main Results:

• The imipenem-resistant strain EA-Z exhibited a distinct OMP profile, notably the loss of a 40 kDa OMP and altered expression of other OMPs.
• A single-step imipenem-resistant mutant (EA-SI8) specifically lost the 40 kDa OMP.
• No significant increase in beta-lactamase activity or imipenem hydrolysis was detected in the resistant strain.
• The OMP profile of EA-Z resembled that of a previously selected imipenem-resistant mutant (EA-SI16).

Conclusions:

• The 40 kDa OMP in Enterobacter aerogenes appears to be essential for the efficient diffusion of imipenem across the outer membrane.
• Alterations in OMP expression, particularly the loss of the 40 kDa OMP, are a likely mechanism contributing to imipenem resistance in this species.
• This finding highlights the importance of OMPs in bacterial susceptibility to antibiotics.