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Active Efflux as a Mechanism of Resistance to Antimicrobial Drugs

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Antimicrobial Drug Resistance

Abstract

Active drug extrusion mediated by efflux transporters is a phenomenon widely observed in both prokaryotic and eukaryotic cells. This process makes a great contribution to intrinsic and acquired resistance in bacteria, fungi and parasites against a broad range of antimicrobial agents and can further interplay with other resistance mechanisms. Drug transporters also function beyond resistance such as those involved in stress response and virulence. There is an ever-growing understanding of drug transporters with respect to their classification, structure, transport mechanisms, regulation and inhibition. This chapter provides an overview of the characteristics and resistance contributions of drug transporters through various examples of clinical significance, with an emphasis on the transporters of the resistance-nodulation-cell division (RND) superfamily in Gram-negative bacteria. The development of clinically-suitable efflux pump inhibitors and novel pump-circumventing antimicrobial drugs continues to be a challenging task. Additionally, the clinical significance of drug transporters highlights the importance of prudent antimicrobial use for minimizing the emergence and spread of antimicrobial drug resistance.

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  1. Human Safety Division, Veterinary Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada

    Xian-Zhi Li M.D., Ph.D.

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  1. Treiber Therapeutics, Cambridge, Massachusetts, USA

    Douglas L. Mayers

  2. Wayne State University School of Medicine, Detroit Medical Center, Detroit, Michigan, USA

    Jack D. Sobel

  3. Centre de recherche en Infectiologie, University of Laval, Quebec City, Canada

    Marc Ouellette

  4. Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, Michigan, USA

    Keith S. Kaye

  5. Infection Control and Prevention Unit of Infectious Diseases, Assaf Harofeh Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

    Dror Marchaim

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Li, XZ. (2017). Active Efflux as a Mechanism of Resistance to Antimicrobial Drugs. In: Mayers, D., Sobel, J., Ouellette, M., Kaye, K., Marchaim, D. (eds) Antimicrobial Drug Resistance. Springer, Cham. https://doi.org/10.1007/978-3-319-46718-4_10

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