Characterizing the mechanism of action of an ancient antimicrobial, manuka honey, against Pseudomonas aeruginosa using modern transcriptomics

Daniel Bouzo, Nural N. Cokcetin*, Liping Li, Giulia Ballerin, Amy L. Bottomley, James Lazenby, Cynthia B. Whitchurch, Ian T. Paulsen, Karl A. Hassan, Elizabeth J. Harry

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Manuka honey has broad-spectrum antimicrobial activity, and unlike traditional antibiotics, resistance to its killing effects has not been reported. However, its mechanism of action remains unclear. Here, we investigated the mechanism of action of manuka honey and its key antibacterial components using a transcriptomic approach in a model organism, Pseudomonas aeruginosa. We show that no single component of honey can account for its total antimicrobial action, and that honey affects the expression of genes in the SOS response, oxidative damage, and quorum sensing. Manuka honey uniquely affects genes involved in the explosive cell lysis process and in maintaining the electron transport chain, causing protons to leak across membranes and collapsing the proton motive force, and it induces membrane depolarization and permeabilization in P. aeruginosa. These data indicate that the activity of manuka honey comes from multiple mechanisms of action that do not engender bacterial resistance. 

IMPORTANCE: The threat of antimicrobial resistance to human health has prompted interest in complex, natural products with antimicrobial activity. Honey has been an effective topical wound treatment throughout history, predominantly due to its broad-spectrum antimicrobial activity. Unlike traditional antibiotics, honey-resistant bacteria have not been reported; however, honey remains underutilized in the clinic in part due to a lack of understanding of its mechanism of action. Here, we demonstrate that honey affects multiple processes in bacteria, and this is not explained by its major antibacterial components. Honey also uniquely affects bacterial membranes, and this can be exploited for combination therapy with antibiotics that are otherwise ineffective on their own. We argue that honey should be included as part of the current array of wound treatments due to its effective antibacterial activity that does not promote resistance in bacteria.

Original languageEnglish
Article numbere00106-20
Number of pages16
JournalmSystems
Volume5
Issue number3
DOIs
Publication statusPublished - May 2020

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Antimicrobial activity
  • Honey
  • Manuka honey
  • Mechanism of action
  • Natural antimicrobial products
  • Pseudomonas aeruginosa
  • RNA-Seq
  • Transcriptomics

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