Development of natural products as novel miticides and anti-virulence agents for the treatment of varroa mites and American foulbrood in honeybees

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Currently, managed and natural ecosystems are threatened by largely unexplained declines in honeybee populations. Since 2006, North American and European beekeepers have lost about one-third of their colonies every year. These colony losses are unprecedented and have endangered the supply of honeybees as pollinators of flowering plants, which has strong economic and ecological implications. These losses also impact non-cultivated plants, good stewards of the land, public concern, and have economic impact on beekeepers and farmers reliant on bees as pollinators. Colony collapse disorder refers to the massive loss of honeybee colonies. Although the causes of this record mortality remain undetermined, it may be due to a combination of a broad suite of stresses on honeybees. Stressed bees have a reduced capacity to resist common larval and adult diseases and secondary infections become more severe. The parasitic mite Varroa destructor, and diseases like American Foulbrood (AFB), are among the factors frequently associated with colony mortality.**1. Hypothesis: (1) Natural products such as essential oils will yield compounds that are highly effective as antivirulence agents for treating AFB infections and Varroa infestations in honeybees.**2. Objectives: The long-term goal is to characterize the extracts of essential oils to (i) develop inhibitors against key bacterial toxins produced by P. larvae for the prevention and treatment of AFB and (ii) to develop miticides effective at controlling V. destructor infestations in honeybees. This will be manifested in the development of a formulation consisting of inhibitory and miticidal compounds extracted and purified from essential oils. This will be achieved with novel methods in molecular modelling, structural biology, and computational chemistry - framed into structure-based drug discovery approaches - combined with experimental validation for AFB-infected and V. destructor-infested larvae. In summary, this research is essential in order to assess the efficacy of natural products to protect bee larvae from these diseases. **************