Antiadhesive Properties of Honey
A large body of evidence is beginning to emerge that describes the antiadhesive or antibiofilm properties of a variety of honeys. Biofilms represent a mode of bacterial growth that is ubiquitous in nature and problematic in the medical environment and in human disease. Some of the best characterized biofilms are those of the oral cavity that comprise the dental plaque. In these biofilms, Streptococcus mutans is regarded as a pioneer colonizer adhering to the salivary pellicle via specific surface adhesins. Studies have demonstrated that manuka honey is bactericidal for this microorganism; however, in addition to this, it can prevent the growth of S. mutans on glass surfaces and saliva-coated hydroxyapatite discs. Multispecies biofilms consisting of S. mutans, S. sobrinus, Lactobacillus rhamnosus, Actinomyces viscosus, Porphyromonas gingvalis and Fusobacterium nucleatum were also inhibited, suggesting that honey could be used as an anticariogenic treatment as an alternative to current treatments such as chlorhexidine, which can have detrimental side effects. However, the application of honeys as anticariogenic treatments warrants further investigation; in particular, to identify specific 'active' components that mediate the antiadhesive effect since using a highly concentrated sugar solution to prevent dental caries seems somewhat counterintuitive.
In infected wounds, biofilms can be incredibly difficult to remove as they are intrinsically resistant to antimicrobial treatment and often systemic antibiotics do not effectively reach the wound bed where the microorganisms reside as a consequence of vascular damage. Generally the topical use of antibiotics to treat infected wounds is not recommended; however, in chronic wounds, topical antibiotics such as mupirocin in MRSA-decolonization regimes might be used. These treatments are often applied for 5–7 days and any remaining bacterial cells following treatment can proliferate and the infection can re-emerge; this is more likely where biofilms are present as these microbial communities are inherently more resistant to treatment. Topical antiseptics or antimicrobials such as honey, while not superseding the use of systemic antibiotics, could be applied simultaneously to accelerate healing of recalcitrant or chronic wounds and ultimately result in lower consumption of systemic antibiotics.
Chronic wounds are associated with the presence of bacterial biofilm and various honeys are effective at inhibiting the development of biofilms comprised of wound-associated pathogens including P. aeruginosa, S. aureus and Streptococcus pyogenes.[39–43] In each case, high concentrations exceeding the MIC for planktonic bacteria were required to completely inhibit biofilm development. The mechanisms by which this is mediated are beginning to be understood and appear to rely in part on the glucose and fructose components of honey. In P. aeruginosa, biofilm inhibition is meditated in a lectin-like manner, suggesting that the sugar components perhaps provide a mechanical means of inhibiting bacterial adherence. Conversely in S. pyogenes this process appears to rely, in part, on the differential expression of two major surface adhesins that are known to have a role in biofilm development. These adhesins (Sof and SfbI) are also known to facilitate streptococcal binding to fibronectin, and reduced expression in the wound environment would impede bacterial binding to host proteins in the wound bed, thus preventing initial colonization; as such, manuka honey could provide an effective prophylactic treatment for wound infection. Importantly manuka honey was able to effectively disrupt and completely remove established biofilms of S. pyogenes in vitro. A recent study by Majtan et al. has demonstrated that MGO is responsible for biofilm disruption, penetrating the bacterial biofilm and killing bacterial cells therein. MGO was observed to penetrate and disrupt biofilms of both Proteus mirabilis and Enterobacter cloacae. The studies did not investigate whether MGO was in fact an antiadhesive, but only described the efficacy of this compound against established biofilms. It is known that sugar components of honeys themselves are antiadhesive in nature, preventing adhesin of bacteria to given surfaces.
As described above, high concentrations of honey are necessary to inhibit and remove biofilms in vitro and this was taken to be the norm as it was in keeping with observations for other types of antimicrobials or antibiotics. However, a recent study with E. coli O157:H7 has demonstrated that this is not necessarily the case. Concentrations as low as 0.5% (w/v) was shown to significantly reduce biofilm biomass by over 95%; this concentration was over ten-times lower than the MIC for this microorganism and 100-times lower than those recorded for other bacteria. Interestingly, the low concentration that prevented E. coli O157:H7 biofilm growth did not inhibit planktonic growth and were not bactericidal suggesting that the antibiofilm properties of honeys are distinct from their bactericidal mode of action (Figure 2). Given that in this study, quorum sensing was also observed to be reduced at these low honey concentrations, it is possible that the observed effect is the consequence of differential expression of adhesins that might be regulated by components of the quorum sensing regulatory network. Indeed, transcriptome analysis demonstrated that the curli genes were repressed, which encode surface structures that mediate binding to host proteins and internalization by eukaryotic cells. In the commensal E. coli K12, biofilm formation was not inhibited by such low levels of honey; however, these organisms lack both the curli genes and the locus of enterocyte effacement suggesting that the observed inhibition of biofilm development for O157:H7 was specifically associated with the expression of these groups of genes. Similar biofilm inhibition (prevention of adhesion, not disruption of established biofilms) and differential gene expression was observed for the sugar components of honey alone, but not for MGO or hydrogen peroxide, suggesting that the sugars may play the most significant antiadhesive function in whole honey. Therefore, it can be hypothesized that the antiadhesive properties of honeys relies on the combined effect of mechanical obstruction as well as differential gene expression in response to different honey components.
Future Microbiol. 2013;8(11):1419-1429. © 2013 Future Medicine Ltd.