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Antimicrobial Drug Efflux Pumps in Enterobacter and Klebsiella

  • Anne Davin-Regli
  • Muriel Masi
  • Suzanne Bialek
  • Marie-Hélène Nicolas-Chanoine
  • Jean-Marie Pagès
Chapter

Abstract

Enterobacter and Klebsiella spp. are recognized as important opportunistic and multidrug-resistant bacterial pathogens and now classified in the ESKAPE microorganism group. These Gram-negative bacteria exhibit a rapid and efficient adaptation to antimicrobial agents and are responsible for several healthcare-associated infections. The modification of the transporters involved in the drug translocation through membrane barrier represents the first line of bacterial defense. Multidrug resistance is primarily due to modifications of membrane transporters involved in the antimicrobial translocation. This results from the activation of several regulatory pathways such as Mar or Ram that control membrane permeability through the expression of porins and efflux pumps. The overexpression of efflux pumps dramatically reduces the intra-bacterial concentration of various classes of antimicrobials, and the extrusion takes place rapidly when the pumps are active. The Enterobacter and Klebsiella prevalence in human infections and the major contribution of efflux for controlling the intracellular concentration of antimicrobials highlight the role of the membrane barrier in bacterial strategies facing our antimicrobial arsenal.

Keywords

Enterobacter Klebsiella Antimicrobial resistance Efflux pumps Outer membrane Porin Activator Repressor Virulence AcrAB-TolC EefABC OqxAB AcrR RamA RamR RarA 

Notes

Acknowledgments

The research leading to the results discussed here was conducted as part of the translocation consortium (www.translocation.eu) and has received support from the Innovative Medicines Initiative joint Undertaking under Grant Agreement n°115525, resources which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP/2007-2013) and EFPIA companies in kind contributions.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Anne Davin-Regli
    • 1
  • Muriel Masi
    • 1
  • Suzanne Bialek
    • 2
    • 3
  • Marie-Hélène Nicolas-Chanoine
    • 2
    • 3
  • Jean-Marie Pagès
    • 1
  1. 1.Transporteurs Membranaires, Chimiorésistance et Drug DesignAix Marseille Univ, IRBA, Facultés de Médecine et de PharmacieMarseilleFrance
  2. 2.Service de MicrobiologieHôpital BeaujonClichyFrance
  3. 3.UMR 1149, Université Paris VIIParisFrance

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