Antibiotic resistance has been described as an ‘apocalyptic’ threat to human health. As resistance to antibiotics is common soon after they are introduced to clinical use, there is little investment in their development. The need for more treatment options has prompted interest in complex natural products as antimicrobials. Honey has been an effective topical wound treatment throughout history, predominantly due to its antimicrobial activity.
Honeys derived from different nectar sources exhibit vastly different levels of activity, and manuka honey has broad-spectrum antimicrobial activity effective against antibiotic resistant pathogens, such as ciprofloxacin-resistant Pseudomonas aeruginosa, and is currently licensed for use in honey-based wound dressings. Unlike traditional antibiotics, bacterial resistance to honey has not been reported, however honey remains underutilised in the clinic largely due to a lack of understanding of its mechanism of action.
Through passaging experiments, we found that honey resistance cannot be induced under conditions that rapidly induced resistance to antibiotics. We hypothesise that this low propensity for resistance is due to multiple modes of action unlike traditional single target antibiotics. We are currently investigating the mechanism of action of honey and its key components using a transcriptomic approach in a model organism, P. aeruginosa. Our results indicate that no single component of honey can account for its total antimicrobial action and that honey causes DNA and oxidative damage, and affects pathways involved in cell motility, central carbon metabolism, and quorum sensing. We found that honey uniquely affects the expression of the P. aeruginosa gene cassette encoding R-pyocins, also known as ‘tailocins’, which are involved in intraspecies competition and explosive cell lysis. Honey also downregulates the expression of various genes involved in maintaining the electron transport chain and causes protons to leak across biological membranes inducing their depolarisation. Taken together, these data argue that honey should be included as part of the current array of wound treatments, due to its effective antibacterial activity that does not engender bacterial resistance.