Mediating a host cell signaling pathway linked to the overwinter mortality offers a promising therapeutic approach for improving bee health

Overwintering mortality is the greatest threat to the supply of healthy bee colonies available for pollination of spring-blooming crops, but efforts to mitigate colony losses are hindered because underlying mechanisms remain poorly understood. In the present study, we identified that sirtuin signaling pathway is the most significantly affected pathway in collapsing overwintering colonies that carried a high prevalence of pathogens and is a convergent signaling hub that links mitochondrial dysfunction and metabolism alterations. We showed that the expression of SIRT1, a major sirtuin regulating energy and immune metabolism, was significantly downregulated in diseased overwintering bees and bees exposed to cold challenge alone. We demonstrated that activation of SIRT1 expression by SRT1720, a SIRT1 activator, could result in increased robustness and lifespan extension of cold-stressed bees. The novel information gained from this study provides a promising avenue for the development of therapeutic strategies for mitigating colony losses, both overwinter and annually. Overall design: The study is divided into four distinct phases. Phase I involved continuous pathogen screening of overwintering bees for four years. Phase II was where RNA-Seq transcriptional profiling of overwintering honey bee host responses to pathogenic infection was conducted. qRT-PCR was performed in Phase III to confirm the results of the differential expression analysis of transcriptome data of selected genes. Lastly, laboratory bioassays were conducted in Phase IV to measure the effects of cold challenges on bee survivorship and stress responses and to assess the effect of SRT1720, an activator of sirtuin 1 (Sirt1) which is a crucial modulator of energy and immune metabolism, on lifespan extension of cold-challenged honey bees.

越冬死亡率是威胁春季开花作物授粉可用健康蜂群供应的最大威胁，然而，由于潜在机制理解不足，减轻蜂群损失的努力受到阻碍。在本研究中，我们鉴定出，携带高发病率病原体的越冬蜂群中，沉默信息调节因子（sirtuin）信号通路是最受影响的通路，它是一个连接线粒体功能障碍和代谢改变的汇聚信号枢纽。我们发现，主要调节能量和免疫代谢的沉默信息调节因子1（SIRT1）的表达在患病越冬蜜蜂以及仅暴露于寒冷挑战的蜜蜂中显著下调。我们证明了通过SRT1720，一种SIRT1激活剂，激活SIRT1表达可以提高冷应激蜜蜂的坚韧性和寿命延长。本研究获得的新信息为开发缓解蜂群损失的治疗策略提供了有希望的途径，无论是越冬还是年度损失。总体设计：该研究分为四个不同的阶段。第一阶段涉及对越冬蜜蜂进行四年连续的病原体筛查。第二阶段是对越冬蜜蜂宿主对病原体感染转录组反应进行RNA-Seq转录组分析。第三阶段通过qRT-PCR确认了选定的基因转录组数据的差异表达分析结果。最后，在第四阶段进行了实验室生物检测，以测量寒冷挑战对蜜蜂存活率和应激反应的影响，并评估sirtuin 1（Sirt1）激活剂SRT1720对受冷挑战的蜜蜂寿命延长的影响。