Unique Mānuka Factor (UMF)-dependent antimicrobial activity of Mānuka honey against respiratory pathogens cannot be explained by sugar and methylglyoxal alone

Respiratory bacterial infections remain a major cause of morbidity and mortality worldwide, and their treatment is increasingly complicated by antimicrobial resistance. Mānuka honey has attracted interest as a potential alternative antimicrobial agent, although the extent to which antibacterial activity varies with Unique Mānuka Factor (UMF™) grade and the relative contribution of methylglyoxal (MGO) remain unclear. In this study, the antimicrobial activity of five UMF™ grades of Mānuka honey (5+, 10+, 12+, 15+ and 20+) was evaluated against clinically relevant respiratory pathogens: methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), Klebsiella pneumoniae and Pseudomonas aeruginosa . MICs were determined using broth microdilution assays. To assess the contribution of osmotic stress, bacterial growth responses were compared with a sugar solution matched to the carbohydrate composition of honey. In addition, MGO-matched control solutions were prepared to examine the contribution of MGO to antimicrobial activity. All Mānuka honey samples inhibited bacterial growth, and MIC values decreased with increasing UMF™ grade. MSSA and MRSA were the most susceptible organisms, whereas higher concentrations were required to inhibit the Gram-negative species. Mānuka honey consistently inhibited bacterial growth more strongly than the matched sugar control, indicating that osmotic effects alone do not explain its antimicrobial activity. Although MGO-matched solutions exhibited antibacterial activity, they were generally less potent than the corresponding whole honey samples. These findings demonstrate that Mānuka honey exhibits UMF-dependent antimicrobial activity against respiratory pathogens and suggest that its antibacterial effects arise from the combined action of MGO and additional components within the honey matrix