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Published on: July 7, 2020
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.
Abstract:
Cephalosporins are widely used in chemotherapy of bacterial infections and resistance mechanisms seriously impair their antibacterial activity. Several resistant strains of Enterobacter aerogenes, a frequently isolated nosocomial pathogen, were analyzed. One isolate exhibited a strong modification of the porin antigenic pattern, especially with an immunological probe directed against an epitope located inside the pore lumen. A strong decrease of cefepime uptake was evidenced for this isolate, similarly to ones observed for porin-deficient strains: these kinetics show a serious alteration of the channel properties which may support cephalosporin resistance. This is the first E. aerogenes isolate using such adaptive response which defines an original enterobacterial answer to cephalosporin.
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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