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Published on: April 25, 2025
Exposure to a Manuka Honey Wound Gel Is Associated With Changes in Bacterial Virulence and Antimicrobial
Jawahir A Mokhtar1,2, Andrew J McBain1, Ruth G Ledder1
1Division of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, School of Health Sciences, The University of Manchester, Manchester, United Kingdom.
Abstract:
The use of manuka honey for the topical treatment of wounds has increased worldwide owing to its broad spectrum of activity towards bacteria in both planktonic and biofilm growth modes. Despite this, the potential consequences of bacterial exposure to manuka honey, as may occur during the treatment of chronic wounds, are not fully understood. Here, we describe changes in antimicrobial susceptibility and virulence in a panel of bacteria, including wound isolates, following repeated exposure (ten passages) to sub-inhibitory concentrations of a manuka honey based wound gel. Changes in antibiotic sensitivity above 4-fold were predominantly related to increased vancomycin sensitivity in the staphylococci. Interestingly, Staphylococcus epidermidis displayed phenotypic resistance to erythromycin following passaging, with susceptibility profiles returning to baseline in the absence of further honey exposure. Changes in susceptibility to the tested wound gel were moderate (≤ 1-fold) when compared to the respective parent strain. In sessile communities, increased biofilm eradication concentrations over 4-fold occurred in a wound isolate of Pseudomonas aeruginosa (WIBG 2.2) as evidenced by a 7-fold reduction in gentamicin sensitivity following passaging. With regards to pathogenesis, 4/8 bacteria exhibited enhanced virulence following honey wound gel exposure. In the pseudomonads and S. epidermidis, this occurred in conjunction with increased haemolysis and biofilm formation, whilst P. aeruginosa also exhibited increased pyocyanin production. Where virulence attenuation was noted in a passaged wound isolate of S. aureus (WIBG 1.6), this was concomitant to delayed coagulation and reduced haemolytic potential. Overall, passaging in the presence of a manuka honey wound gel led to changes in antimicrobial sensitivity and virulence that varied between test bacteria.
Insights
Repeated exposure to manuka honey wound gel altered bacterial antimicrobial sensitivity and virulence. Some bacteria showed increased resistance, while others developed enhanced virulence, highlighting the complex effects of honey-based treatments on wound pathogens.
Area of Science:
- Microbiology
- Wound Healing
- Antimicrobial Resistance
Background:
- Manuka honey is widely used for topical wound treatment due to its broad-spectrum antimicrobial activity.
- The effects of repeated exposure to manuka honey on bacterial antimicrobial susceptibility and virulence are not fully understood.
- Chronic wounds present a unique environment where bacteria may encounter sub-inhibitory concentrations of therapeutic agents.
Purpose of the Study:
- To investigate the impact of repeated exposure to a manuka honey-based wound gel on bacterial antimicrobial susceptibility.
- To assess changes in bacterial virulence factors following sub-inhibitory manuka honey wound gel exposure.
- To evaluate alterations in both planktonic and biofilm bacterial communities.
Main Methods:
- Bacteria, including wound isolates, were subjected to ten passages in sub-inhibitory concentrations of a manuka honey wound gel.
- Antimicrobial susceptibility testing was performed for various antibiotics and the wound gel itself.
- Virulence assays were conducted, including haemolysis, biofilm formation, pyocyanin production, and coagulation assays.
Main Results:
- Increased vancomycin sensitivity was observed in staphylococci; *Staphylococcus epidermidis* developed transient erythromycin resistance.
- A *Pseudomonas aeruginosa* isolate showed increased resistance to gentamicin (7-fold reduction in sensitivity) and enhanced biofilm eradication concentrations.
- Four out of eight bacteria exhibited enhanced virulence, with increased haemolysis and biofilm formation in *Pseudomonas* species and *S. epidermidis*. *P. aeruginosa* also showed increased pyocyanin production.
Conclusions:
- Repeated exposure to manuka honey wound gel can induce changes in antimicrobial susceptibility and virulence in bacteria.
- The observed effects vary significantly between different bacterial species and strains.
- These findings underscore the need for careful monitoring during chronic wound treatment with honey-based products to mitigate potential resistance and virulence changes.
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