Mechanism of the antibacterial activity and resistance of polymyxins

Matthew D Johnson, Roger L Nation, Jian Li

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

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.  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.
Original languageEnglish
Title of host publicationAntimicrobial Drug Resistance
Subtitle of host publicationMechanisms of Drug Resistance
EditorsDouglas L Mayers, Jack D Sobel, Marc Ouellette, Keith S Kaye, Dror Marchaim
Place of PublicationCham Switzerland
PublisherSpringer
Pages333-344
Number of pages12
Volume1
Edition2
ISBN (Electronic)9783319467184
ISBN (Print)9783319467160
DOIs
Publication statusPublished - 2017

Keywords

  • Lipid A
  • lipopolysaccharide (LPS) • Active efflux
  • Capsule polysaccharide • outer membrane
  • Gram-negative bacteria
  • Knock-out mutations

Cite this

Johnson, M. D., Nation, R. L., & Li, J. (2017). Mechanism of the antibacterial activity and resistance of polymyxins. In D. L. Mayers, J. D. Sobel, M. Ouellette, K. S. Kaye, & D. Marchaim (Eds.), Antimicrobial Drug Resistance: Mechanisms of Drug Resistance (2 ed., Vol. 1, pp. 333-344). Cham Switzerland: Springer. https://doi.org/10.1007/978-3-319-46718-4_23
Johnson, Matthew D ; Nation, Roger L ; Li, Jian. / Mechanism of the antibacterial activity and resistance of polymyxins. Antimicrobial Drug Resistance: Mechanisms of Drug Resistance. editor / Douglas L Mayers ; Jack D Sobel ; Marc Ouellette ; Keith S Kaye ; Dror Marchaim. Vol. 1 2. ed. Cham Switzerland : Springer, 2017. pp. 333-344
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Johnson, MD, Nation, RL & Li, J 2017, Mechanism of the antibacterial activity and resistance of polymyxins. in DL Mayers, JD Sobel, M Ouellette, KS Kaye & D Marchaim (eds), Antimicrobial Drug Resistance: Mechanisms of Drug Resistance. 2 edn, vol. 1, Springer, Cham Switzerland, pp. 333-344. https://doi.org/10.1007/978-3-319-46718-4_23

Mechanism of the antibacterial activity and resistance of polymyxins. / Johnson, Matthew D; Nation, Roger L; Li, Jian.

Antimicrobial Drug Resistance: Mechanisms of Drug Resistance. ed. / Douglas L Mayers; Jack D Sobel; Marc Ouellette; Keith S Kaye; Dror Marchaim. Vol. 1 2. ed. Cham Switzerland : Springer, 2017. p. 333-344.

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

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N2 - 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.  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.

AB - 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.  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.

KW - Lipid A

KW - lipopolysaccharide (LPS) • Active efflux

KW - Capsule polysaccharide • outer membrane

KW - Gram-negative bacteria

KW - Knock-out mutations

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DO - 10.1007/978-3-319-46718-4_23

M3 - Chapter (Book)

SN - 9783319467160

VL - 1

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EP - 344

BT - Antimicrobial Drug Resistance

A2 - Mayers, Douglas L

A2 - Sobel, Jack D

A2 - Ouellette, Marc

A2 - Kaye, Keith S

A2 - Marchaim, Dror

PB - Springer

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ER -

Johnson MD, Nation RL, Li J. Mechanism of the antibacterial activity and resistance of polymyxins. In Mayers DL, Sobel JD, Ouellette M, Kaye KS, Marchaim D, editors, Antimicrobial Drug Resistance: Mechanisms of Drug Resistance. 2 ed. Vol. 1. Cham Switzerland: Springer. 2017. p. 333-344 https://doi.org/10.1007/978-3-319-46718-4_23