Exposure to a Manuka Honey Wound Gel Is Associated With Changes in Bacterial Virulence and Antimicrobial Susceptibility

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.

Honey: Another Alternative in the Fight against Antibiotic-Resistant Bacteria?

“…This study recognized that honey possesses antibacterial properties upon resistant bacteria, and can also promote effective wound healing [93]. Following this study, a significant amount of work using manuka honey confirmed its effects against MRSA in vitro [24,[94][95][96][97][98][99][100] and in vivo [101], vancomycin-resistant S. aureus [91], and vancomycin-resistant enterococci (VRE) [100]. MRSA and VRE are considered the foremost pathogens that often infect chronic wounds in the earlier stages [96].…”

“…More recently, Mokhtar et al evidenced that long-term exposure of different strains of S. aureus, S. pyogenes, P. aeruginosa, E. coli, MRSA and S. epidermidis to manuka honey was not able to generate isolates with a reduced susceptibility to honey following a similar time frame in which resistance to macrolides was generated [97]. Moreover, it was suggested that the iron chelation capacity of manuka honey affects multiple diverse physiological processes in bacteria and would contribute to the lack of bacterial resistance to honey [75].…”

Saudi Honey: A Promising Therapeutic Agent for Treating Wound Infections

“…This was the result of observed antimicrobial properties of methylglyoxal, which can promote wound healing and exhibit potent activity against various planktonic and biofilm-forming Gram-positive and Gram-negative pathogenic bacteria, including wound pathogens [19]. Interestingly and importantly, increased in vitro sensitivity was observed in bacterial strains treated with Manuka honey to clinically used antibiotics, compared with untreated bacteria [20].…”

“…However, resistance to silver was observed in certain wound-infecting bacteria, such as E. coli and Acinetobacter baumannii [17]. Manuka honey, as a natural alternative, was successful in preventing biofilm formation by P. aeruginosa and S. aureus and limited the possibility of developing resistance, making its potential therapeutic use in treating wound infections very promising [18][19][20].…”

Evaluation of antimicrobial and anticancer activities of three peptides identified from the skin secretion of <italic>Hylarana latouchii</italic>

“…The antibiofilm activity of peptides was evaluated by the minimum biofilm inhibitory concentration (MBIC) and the minimum biofilm eradication concentration (MBEC) assays against S. aureus and P. aeruginosa as previously described [26,27] with some modifications. For the MBIC assay, 1 × 10 6 cfu/ml bacterial culture in Muellar-Hinton Broth (MHB) was mixed with antimicrobial peptides (1-512 mg/l) in a 96-well plate, followed by incubation for 24 h at 37C at 120 rpm.…”