The threat of antimicrobial resistance to human health has prompted interest in complex, natural products as antimicrobials. Honey has been an effective topical wound treatment throughout history, predominantly due to its broad-spectrum antimicrobial activity. Unlike traditional antibiotics, bacterial resistance to the inhibitory and killing effects of honey has not been reported. Despite this, honey remains underutilised in the clinic in part due to a lack of understanding of its mechanism of action. Honeys derived from different nectar sources exhibit vastly different levels of activity, and manuka honey (from Leptospermum scoparium trees) has broad-spectrum antimicrobial activity effective against antibiotic resistant pathogens and is currently licensed for use in honey dressings to treat wounds.
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 honey affects multiple processes in bacteria, and that no single component of honey can account for its total antimicrobial action. Honey affects the expression of genes in the SOS response, oxidative damage and quorum sensing. It also 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 and this may 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.