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

Authors

  • J.-P. Lavigne,

    1.  UMR-MD-1, Facultés de Médecine et de Pharmacie, IFR 88, Université de la Méditerranée, Marseille
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    • Present address: INSERMU1047, Université Montpellier 1, UFR de Médecine, Nîmes, France.

  • A. Sotto,

    1.  Institut National de la Santé et de la Recherche Médicale, U1047, Université Montpellier 1, UFR de Médecine, Nîmes
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  • M.-H. Nicolas-Chanoine,

    1.  Service de Microbiologie, Hôpital AP-HP Beaujon, Clichy
    2.  Institut National de la Santé et de la Recherche Médicale, U773 Centre de Recherche Biomédicale Bichat-Beaujon, Université Paris 7, Faculté de Médecine D. Diderot, Paris
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  • N. Bouziges,

    1.  Institut National de la Santé et de la Recherche Médicale, U1047, Université Montpellier 1, UFR de Médecine, Nîmes
    2.  Laboratoire de Bactériologie, Groupe Hospitalo-Universitaire de Carémeau, Nîmes, France
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  • G. Bourg,

    1.  Institut National de la Santé et de la Recherche Médicale, U1047, Université Montpellier 1, UFR de Médecine, Nîmes
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  • A. Davin-Regli,

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

    1.  UMR-MD-1, Facultés de Médecine et de Pharmacie, IFR 88, Université de la Méditerranée, Marseille
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Corresponding author: J.-M. Pagès, UMR-MD1, Transporteurs Membranaires, Chimiorésistance et Drug Design, Faculté de Médecine, IFR 88, 27 Bd Jean Moulin, 13385 Marseille cedex 05, France
E-mail: jean-marie.pages@univmed.fr

Abstract

Clin Microbiol Infect 2012; 18: 539–545

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.

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