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

Bouzo, Daniel, Cokcetin, Nural N., Li, Liping, Ballerin, Giulia, Bottomley, Amy L., Lazenby, James, Whitchurch, Cynthia B. ORCID:, Paulsen, Ian T., Hassan, Karl A. and Harry, Elizabeth J. (2020) Characterizing the mechanism of action of an ancient antimicrobial, manuka honey, against pseudomonas aeruginosa using modern transcriptomics. mSystems, 5 (3). ISSN 2379-5077

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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.

Item Type: Article
Additional Information: Funding Information: We thank Comvita New Zealand for supplying the manuka honey sample. Flow cytometry was performed at the UTS Microbial Imaging Facility. We also thank Merilyn Manley-Harris for advice on the formulation of artificial honey, Helen Zgurskaya for providing the hyperporinated P. aeruginosa strain, Shona Blair for constructive criticism and advice, and Jordana Goth for assistance with knockout screening. This work was supported by a UTS Doctoral Scholarship awarded to Daniel Bouzo. D.B., E.H., K.H., L.L., and N.C. contributed to the conception and design of the work. D.B., N.C., E.H., L.L., K.H., G.B., J.L., and A.B. contributed to the acquisition, analysis, and interpretation of data for the work. The paper was written by D.B. and N.C. and critically revised by E.H., L.L., K.H., I.P., A.B., and C.W. Comvita New Zealand provided materials (honey samples) for the work described in the manuscript. We declare that the research was conducted in the absence of any commercial, financial, or personal relationships that could be construed as a potential conflict of interest. Funding Information: This work was supported by a UTS Doctoral Scholarship awarded to Daniel Bouzo. Publisher Copyright: Copyright © 2020 Bouzo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Uncontrolled Keywords: antimicrobial activity,honey,manuka honey,mechanism of action,natural antimicrobial products,pseudomonas aeruginosa,rna-seq,transcriptomics,microbiology,physiology,biochemistry,ecology, evolution, behavior and systematics,modelling and simulation,molecular biology,genetics,computer science applications,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2400/2404
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 03 Nov 2022 12:30
Last Modified: 07 Nov 2022 00:49
DOI: 10.1128/mSystems.00106-20

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