## 4 Antimicrobial Properties of Honey
The Manuka honey antibacterial effect seems to be incompatible with peroxide-mediated activity, as MGO supplementation has been shown to impede GOx activity in non-Manuka honey by morphological damage and the formation of a glycated derivative structure. As a result, GOx-modulated H\({}_{2}\)O\({}_{2}\) production was significantly compromised in a dose-proportional fashion [94]. However, an interaction between peroxide and non-peroxide systems has been described by [PERSON] et al., who studied the antibacterial activity of honey in relation not only to its content of MGO and analogous \(\alpha\)-dicarbonyl compounds but also to their conversion into different free radicals in the presence of either hydrogen peroxide or amino acids (specifically arginine and lysine) [95]. [PERSON] et al. also reported how MGO structurally inactivates other peptides deemed responsible for the therapeutical applications of honey in dermatology, such as the beceptible defensin-1, with possible impaired antibacterial activity [96]. Studies conducted on non-Manuka honey suggest that defensin-1 might be a crucial element to the antibacterial activity of honey of some geographical and botanical origin while being irrelevant in other samples. Defensin-1 levels in honeybee honey do not seem to influence the antibacterial effect on cultured _S. aureus_, which is responsible for many nosocomial infections. This was confirmed by the uncompromised antibacterial activity despite protein inactivation by peptidase [76]. In contrast, proteinase K-treated Greek honeys had their microbiological properties negatively impacted, as demonstrated by higher honey concentrations needed to achieve the same bacterial inhibition (i.e., higher MIC) [97]. Nevertheless, besides the irregular antibacterial function reported in the discordant literature, this peptide could give a pivotal contribution to the skin regenerative effect traditionally shown by honey and royal jelly. The defensin-1-induced wound-healing advancement is achieved in vitro by significantly increased matrix metalloproteinase-9 (MMP-9) release and consequently enhanced keratinocytes chemotaxis and neo-vascularisation in vivo [98]. This restorative mechanical process is fundamental to the re-establishment of an effective skin barrier following epithelial cell migration after an injury; thus, such encouraging results offer a further explanation for the use of bee products in wound medicine. In the struggle against hospital-acquired infections, biofilm eradication from chronic wounds represents a substantial challenge [99]. Heather honey showed analogous effectiveness to Manuka honey against the biofilm formation from different species, namely _Acinetobacter baumaniii_ (_A. baumaniii_), _E. coli_, _Salmonella enteritidis_ (_S. enteritidis_), and _P. aeruginosa_. A shared key element in the inhibition of the _P. aeruginosa_ biofilm for both the honey varieties could be benzoic acid, which has been predicted by molecular docking to efficiently bind the bacterial enzyme _Pa_DsbA1. In doing so, it would alter the protein structural arrangement, hence compromising the biological functionality of fimbiae, flagellae, and adhesion factors, which are crucial for biofilm establishment. However, heather honey promoted _E. faecalis_ and _Klebsiella pneumoniae (K. pneumoniae)_ biofilms, while Manuka honey was ineffective on _S. aureus_[100]. This different susceptibility of the bacterial species to honey of different botanical origin could be considered when evaluating which honey variety to use to treat a given infected wound. Portuguese heather honey effectively inhibited _Candidata tropicalis_ (_C. tropicalis_) planktonic population at a lower concentration (MIC 12.5% (_w/v_), minimum fungicidal concentration 50% (_w/v_)) than Manuka honey (MIC 25% (_w/v_), MFC 50% (_v_/v_)). The two honey varieties were also compared on their antimicrobial action on single and multi-species biofilms of _C. tropicalis_ with _P. aeruginosa_. A significant reduction in the cell viability of _C.