RT Journal Article
SR Electronic
T1 Characterising the mechanism of action of an ancient antimicrobial, honey, using modern transcriptomics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.12.946830
DO 10.1101/2020.02.12.946830
A1 Daniel Bouzo
A1 Nural N. Cokcetin
A1 Liping Li
A1 Giulia Ballerin
A1 Amy L. Bottomley
A1 James Lazenby
A1 Cynthia B. Whitchurch
A1 Ian T. Paulsen
A1 Karl A. Hassan
A1 Elizabeth J. Harry
YR 2020
UL http://biorxiv.org/content/early/2020/02/13/2020.02.12.946830.abstract
AB 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 induces membrane depolarisation and permeabilisation 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 underutilised 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.