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Mechanism of the Antibacterial Activity and Resistance of Polymyxins

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Antimicrobial Drug Resistance

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Abstract

Discovered in the 1940s, polymyxins are antimicrobial peptides produced by the Gram-positive soil bacterium, Paenibacillus polymyxa, which biosynthesizes polymyxins using non-ribosomal peptide synthetase enzymes [1–3]. Polymyxin B and E (polymyxin E was originally named colistin but was determined to have an identical structure) were used clinically in the late 1950s against Gram-negative bacterial infections [4, 5]. However, nephrotoxic and neurotoxic effects of polymyxin treatment became evident, causing a decline in the use of the polymyxins in the 1970s [6]. Soon, newer antibiotics, such as the aminoglycosides, replaced polymyxins in the clinic. However, since the early 2000s the emergence of multidrug-resistant (MDR) Gram-negative organisms, combined with a lack of novel antimicrobial agents, has led to the resurgence of interest in polymyxins as a last-line treatment ([7–10]; Nation and Li 2009).

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Authors and Affiliations

  1. Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia

    Matthew D. Johnson, Roger L. Nation Ph.D. & Jian Li Ph.D.

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  1. Matthew D. Johnson
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  2. Roger L. Nation Ph.D.
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  3. Jian Li Ph.D.
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Correspondence to Roger L. Nation Ph.D. or Jian Li Ph.D. .

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Editors and Affiliations

  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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Johnson, M.D., Nation, R.L., Li, J. (2017). Mechanism of the Antibacterial Activity and Resistance of Polymyxins. 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_23

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