Translational plausibility of honey-derived antimicrobial biomaterials against biofilm-associated infections

Chronic biofilm-associated infections drive antimicrobial resistance (AMR) via prolonged systemic antibiotic therapy that is often ineffective. Honeys from Apis mellifera and stingless bees (Meliponini) exhibit antimicrobial and anti-biofilm activity via complementary mechanisms: osmotic stress, low pH, hydrogen peroxide, methylglyoxal, bee defensin-1, and phenolic and organic compounds. This is most effective when concentrated at the application site. Yet honey therapeutics are often framed as systemic nutraceuticals despite biologically incoherent pharmacokinetics. We propose translational plausibility, an analytical framework built on four interdependent dimensions: spatial, temporal, dose, and compositional coherence that distinguishes microbiologically defensible interventions from speculative ones, applicable beyond honey to natural-product antimicrobials. Applied to honey, the framework identifies topical, localized application as the only translationally coherent clinical route. Reframed as ecological therapeutic biomaterials, honeys address interconnected AMR priorities: disrupting polymicrobial ESKAPE biofilms, preserving distant microbiotas, reducing systemic antibiotic use in wound care, potentiating antibiotics, and supporting stewardship. Planetary health benefits, pollinator conservation, meliponiculture, and equitable access emerge as corollaries, not primary justification.