Abstract
Humans use natural products to treat disease; similarly, some insects use natural products produced by Actinobacteria to combat infectious pathogens. Honey bees, Apis mellifera, are ecologically and economically important for their critical role as plant pollinators and are host to diverse and potentially virulent pathogens that threaten hive health. Here, we provide evidence that Actinobacteria that can suppress pathogenic microbes are associated with A. mellifera. We show through culture-dependent approaches that Actinobacteria in the genus Streptomyces are commonly isolated from foraging bees, and especially common in pollen stores. One strain, isolated from pollen stores, exhibited pronounced inhibitory activity against Paenibacillus larvae, the causative agent of American foulbrood. Bioassay-guided HPLC fractionation, followed by NMR and mass spectrometry, identified the known macrocyclic polyene lactam, piceamycin that was responsible for this activity. Further, we show that in its purified form, piceamycin has potent inhibitory activity toward P. larvae. Our results suggest that honey bees may use pollen-derived Actinobacteria and their associated small molecules to mediate colony health. Given the importance of honey bees to modern agriculture and their heightened susceptibility to disease, the discovery and development of antibiotic compounds from hives could serve as an important strategy in supporting disease management within apiaries.
Highlights
Natural products play a critical role in human health, serving as drugs or drug leads that are used to treat diverse human afflictions, including cancer and hypertension (Newman and Cragg, 2020)
Newly eclosed bees, adult bees found in hives, adult bees found foraging, swarming bees, commercial bees, empty combs, propolis, honey, and pollen stores were all sampled for the presence of Actinobacteria
We identified a known antibiotic produced by a Streptomyces isolated from the pollen stores of honey bees
Summary
Natural products play a critical role in human health, serving as drugs or drug leads that are used to treat diverse human afflictions, including cancer and hypertension (Newman and Cragg, 2020). Honey Bee Associated Streptomyces Antibiotics analysis of sequenced genomes has revealed that past efforts have overlooked many potentially useful compounds (Bachmann et al, 2014; Baltz, 2017) Despite their critical importance to human health, our understanding of the function of these secondary metabolites in their natural context is limited. One of the most well-studied systems is the complex and ancient symbiosis associated with fungusgrowing ants Many of these ants engage in an obligate mutualism with Actinobacteria in the genus Pseudonocardia, which produce antibiotics that help defend against parasitic infections of the mutualist fungus that the ants cultivate for food (Currie and Scott, 1999; Currie et al, 2002; Cafaro et al, 2011; Li et al, 2018). A recent study of 2,561 insects spanning 15 orders and more than 10,000 Streptomyces isolates suggests that these types of defensive mutualisms are likely more widespread than currently recognized and may serve as a source for discovering novel natural products that could serve as antibiotic drug leads (Chevrette et al, 2019)
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