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

Clin Microbiol Infect. 2012 Jun;18(6):539-45. doi: 10.1111/j.1469-0691.2011.03607.x. Epub 2011 Aug 29.

Abstract

Imipenem-susceptible E. aerogenes isolates exhibiting extended spectrum β-lactamases, target mutations and a basal efflux expression, were identified in five patients. After imipenem treatment, imipenem-intermediate susceptible (IMI-I) or resistant (IMI-R) isolates emerged in these patients. Alteration in porin synthesis and increase in efflux expression were observed in the IMI-I isolates whereas complete loss of the porins, LPS alteration and efflux overexpression were observed in the IMI-R isolates. Bacterial virulence of the strains was investigated by the Caenorhabditis elegans model. The IMI-R isolates were shown to be significantly less virulent than the IMI-susceptible or IMI-I isolates. The pleiotropic membrane alteration and its associated fitness burden exhibited by E. aerogenes isolates influence their antibiotic resistance and their virulence behaviour. These findings highlight the balance between the low permeability-related resistance and virulence and their relationships with the treatment of resistant pathogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / metabolism*
  • Anti-Bacterial Agents / pharmacology
  • Biological Transport
  • Caenorhabditis elegans / microbiology
  • Cell Membrane / physiology*
  • Drug Resistance, Bacterial*
  • Enterobacter aerogenes / drug effects*
  • Enterobacter aerogenes / isolation & purification
  • Enterobacter aerogenes / pathogenicity
  • Enterobacteriaceae Infections / microbiology*
  • Humans
  • Imipenem / metabolism*
  • Imipenem / pharmacology
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Permeability
  • Porins / genetics
  • Porins / metabolism
  • Virulence
  • Virulence Factors / metabolism*
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Mutant Proteins
  • Porins
  • Virulence Factors
  • Imipenem
  • beta-Lactamases