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

目前，受管理的自然生态系统受到蜜蜂数量大量不明原因下降的威胁。自2006年以来，北美和欧洲的养蜂人每年都会失去大约三分之一的蜂群。这些蜂群损失是前所未有的，并危及蜜蜂作为开花植物授粉者的供应，这具有强烈的经济和生态影响。这些损失还影响到非种植植物、土地的良好管理者、公众的关注，并对养蜂人和依赖蜜蜂授粉的农民产生经济影响。蜂群衰竭失调是指蜂群的大量损失。虽然这一创纪录的死亡率的原因仍然没有确定，它可能是由于一系列广泛的压力对蜜蜂的组合。应激蜜蜂抵抗常见幼虫和成虫疾病的能力降低，继发感染变得更加严重。寄生螨狄斯瓦螨（Varroa destructor）和美国臭幼虫病（American Foulbrood，AFB）等疾病是经常与菌落死亡率相关的因素。1.假设：（1）天然产品如精油将产生作为抗病毒剂的高效化合物，用于治疗蜜蜂中的AFB感染和瓦螨属侵染。2.目的：长期目标是对精油提取物进行表征，以（i）开发针对由P. larvae产生的关键细菌毒素的抑制剂，用于预防和治疗AFB，以及（ii）开发有效控制蜜蜂中V. destructor感染的杀螨剂。这将体现在一种由从精油中提取和纯化的抑制和杀螨化合物组成的制剂的开发中。这将通过分子建模，结构生物学和计算化学中的新方法来实现-框架为基于结构的药物发现方法-结合对AFB感染和V. destructor感染幼虫的实验验证。总之，这项研究对于评估天然产品保护蜜蜂幼虫免受这些疾病的影响至关重要。**************

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. **************