The fundamental feature of "active honeys" is the presence and concentration of antibacterial compounds. Currently identified compounds and factors have been described in several review papers without broader interpretation or links to the processes for their formation. In this review, we indicate that the dynamic, antagonistic/competitive microbe-microbe and microbe-host interactions are the main source of antibacterial compounds in honey. The microbial colonization of nectar, bees and honey is at the center of these interactions that in consequence produce a range of defence molecules in each of these niches. The products of the microbial interference and exploitive competitions include antimicrobial peptides, antibiotics, surfactants, inhibitors of biofilm formation and quorum sensing. Their accumulation in honey by horizontal transfer might explain honey broad-spectrum, pleiotropic, antibacterial activity. We conclude that honey is an ecological reservoir of antibacterial compounds produced by antagonistic microbial interactions in plant nectars, honey and honey bee. Thus, refocusing research on secondary metabolites resulting from these microbial interactions might lead to discovery of new antibacterial compounds in honey that are target-specific, i.e., acting on specific cellular components or inhibiting the essential cellular function.
Keywords: antimicrobial compounds; bacteriocins; bee antimicrobial peptides; honey; microbiota; mode of action; pathogenesis-related proteins; siderophores; spectrum of activity; surfactants.