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Membrane permeability, a pivotal function involved in antibiotic resistance and virulence in Enterobacter aerogenes

J-P Lavigne1, A Sotto, M-H Nicolas-Chanoine

  • 1UMR-MD-1, Facultés de Médecine et de Pharmacie, IFR 88, Université de la Méditerranée, Marseille, France.

Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases
|September 3, 2011
PubMed

Insights

Emergence of imipenem resistance in E. aerogenes during treatment is linked to membrane alterations. These changes reduce bacterial virulence, highlighting a trade-off between resistance and fitness in pathogens.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pathogen Resistance

Background:

  • Enterobacter aerogenes can develop resistance to carbapenem antibiotics like imipenem.
  • Mechanisms of resistance include extended spectrum beta-lactamases, target mutations, and efflux pumps.

Purpose of the Study:

  • To investigate the mechanisms of imipenem resistance development in E. aerogenes.
  • To evaluate the impact of resistance mechanisms on bacterial virulence.

Main Methods:

  • Identification and characterization of E. aerogenes isolates from patients undergoing imipenem treatment.
  • Analysis of porin synthesis, lipopolysaccharide (LPS) alteration, and efflux pump expression.
  • Assessment of bacterial virulence using the Caenorhabditis elegans model.

Main Results:

  • Imipenem-susceptible isolates evolved to imipenem-intermediate (IMI-I) or imipenem-resistant (IMI-R) phenotypes after treatment.
  • IMI-I isolates showed altered porin synthesis and increased efflux, while IMI-R isolates had complete porin loss, LPS alteration, and efflux overexpression.
  • IMI-R isolates exhibited significantly reduced virulence compared to susceptible or IMI-I isolates.

Conclusions:

  • Pleiotropic membrane alterations in E. aerogenes contribute to both antibiotic resistance and reduced virulence.
  • A fitness cost is associated with the development of low-permeability-related resistance.
  • Understanding the balance between resistance and virulence is crucial for treating resistant bacterial infections.

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