Flagellum Removal by a Nectar Metabolite Inhibits Infectivity of a Bumblebee Parasite

Plant secondary metabolites can act as natural “medicines” for animals against parasites. Some nectar metabolites, for example, reduce parasite infections in bees. Understanding these interactions is urgent, as bees provide critical pollination services but are threatened by interacting stressors including diseases. Declining plant diversity through anthropogenic landscape change could reduce the availability of medicinal nectar plants for pollinators, exacerbating their decline. Existing studies are, however, limited by (i) a lack of mechanistic insights into how plant metabolites affect pollinator diseases, and (ii) the restriction to few, commercially available chemicals, thereby potentially neglecting plants with the biggest antiparasitic effects. To rapidly identify plants with the greatest potential as natural bee medicines, we developed a bioactivity- directed-fractionation assay for nectar metabolites. We evaluated 17 important nectar plants against the common bumblebee pathogen Crithidia bombi (Trypanosomatidae). The most bioactive species was heather (Calluna vulgaris), the second most productive UK nectar plant. We identified 4-(3-oxobut-1-enylidene)- 3,5,5-trimethylcyclohex-2-en-1-one (callunene) from heather nectar as potent inhibitor of C. bombi. Wild bumblebees (Bombus terrestris) foraging on heather ingest callunene at concentrations causing complete C. bombi inhibition. Feeding on callunene was prophylactic against infections. We show C. bombi establishes infections by flagellar anchoring to the ileum epithelium. Short-term callunene exposure induced flagellum loss in C. bombi choanomastigotes, resulting in a loss of infectivity. We conclude plant secondary metabolites can disrupt parasite flagellum attachment, revealing a mechanism behind their prophylactic effects. The decline of heathlands reduces the availability of natural bee “medicine” and could exacerbate the contribution of diseases to pollinator declines.