In vivo modification of porin activity conferring antibiotic resistance to Enterobacter aerogenes

J Chevalier1, J M Pagès, M Malléa

  • 1CJF 9606 INSERM, Université de la Méditerannée, Marseille Cedex 05, 13385, France.

Insights

This study identifies a novel cephalosporin resistance mechanism in Enterobacter aerogenes. A specific porin modification significantly reduced cefepime uptake, indicating an adaptive response contributing to antibiotic resistance.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pharmacology

Background:

  • Cephalosporins are crucial antibiotics for bacterial infections.
  • Antibiotic resistance, particularly in nosocomial pathogens like Enterobacter aerogenes, is a growing global health concern.
  • Mechanisms of cephalosporin resistance often involve alterations in bacterial outer membrane proteins, such as porins.

Purpose of the Study:

  • To investigate the mechanisms of cephalosporin resistance in clinical isolates of Enterobacter aerogenes.
  • To identify specific alterations in porin structure and function contributing to reduced antibiotic susceptibility.
  • To characterize a novel adaptive response in Enterobacter aerogenes conferring resistance to cephalosporins.

Main Methods:

  • Analysis of resistant Enterobacter aerogenes strains.
  • Immunological probing of porin antigenic patterns.
  • Measurement of cefepime uptake kinetics.
  • Comparison with porin-deficient strains.

Main Results:

  • One Enterobacter aerogenes isolate showed significant modification of its porin antigenic pattern.
  • This modification, particularly affecting an internal pore epitope, led to a marked decrease in cefepime uptake.
  • The observed changes in channel properties are similar to those in porin-deficient strains, suggesting impaired antibiotic transit.

Conclusions:

  • The identified porin modification represents a novel adaptive response in Enterobacter aerogenes.
  • This mechanism contributes to cephalosporin resistance by altering porin channel function and reducing drug uptake.
  • This finding highlights an original enterobacterial strategy for overcoming cephalosporin chemotherapy.

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