Genetic and environmental effects on virulence of European foulbrood, a bacterial pathogen of honey bees

蜜蜂（Apis属）是经济上重要的作物传粉者以及蜂蜜的生产者。它们受到新出现的疾病和管理做法变化的重大威胁，这些变化对它们的饲养环境产生不利影响。在英国，最具破坏性的疾病之一，只能通过破坏蜂巢来治疗，是美国臭蜂病（AFB）。之前的一个约克-费拉BBSRC CASE学生项目开发了一种多位点序列分型（MLST）方案，用于美国恶臭病菌的病原体类芽孢杆菌幼虫。自2014年以来，对疫情进行了常规分型，我们试图在这项工作的基础上确定这些信息可用于预测AFB发生和传播的程度。如果不及时治疗，AFB会杀死一群蜜蜂。孢子被喂给幼虫，幼虫在肠道中发芽，在蜂巢细胞被“封顶”后，细菌繁殖，最终杀死幼虫，形成数百万个抗性孢子，这些孢子随后分散开来。在英国有许多基因型，它们显示出高水平的菌株变异，由MLST和比较基因组学定义。最近的研究表明，病原体遇到的肠道微生物组的群落多样性和竞争过程对于决定感染的进展和结果很重要。反过来，肠道微生物群是由外部环境因素决定的，比如食物资源。因此，我们假设蜂箱中AFB感染的结果是疾病菌株基因型和幼虫肠道环境之间复杂的相互作用。该项目的总体目标是将MLST确定的克隆复合物（CC）内部和之间的基因型与疾病症状及其发生的环境联系起来，并将其转化为检查和监测计划，进一步有助于控制这种破坏性疾病。该奖学金将涉及四个研究领域：1)群体遗传学：基于先前的分析（Morrissey et al. 2015；见下文），并使用随后使用MLST收集的数据，AFB爆发的时空模式是什么？克隆复合体（CCs）能否可靠地用于区分新爆发和再感染？2)比较基因组学：从已知分布和疾病严重程度的cc中收集的分离株，将确定基因组序列并对与毒力相关的基因进行广泛分析。3)环境基因组学：哪些环境因素影响疾病流行和严重程度的模式？该学生将研究蜜蜂宿主肠道微生物组，以及它们与特定类型AFB感染的关系。4)实际应用：研究可以通过多种方式影响AFB的筛选和管理。如果MLST类型可以预测疾病的严重程度，那么可以优先销毁疫情，并推荐后续检查制度。更复杂的环境因素，如食物资源和肠道微生物群，可以预测哪些菌株成功感染蜂巢，或者一旦感染形成，疾病的严重程度。学生将确定和发展最有希望的实际减轻疾病的途径。该项目将结合约克大学的基因组学技术和分析，并有机会在Fera与蜜蜂单位合作进行实验，以及他们最先进的培养和操纵AFB的设施。

Honey bees (Genus Apis) are economically important pollinators of crops as well as producers of honey. They are under significant threats from emerging diseases and changes in management practices that adversely affect their feeding environment. In the UK, one of the most damaging diseases, treatable only by hive destruction, is American Foulbrood (AFB). A previous York-Fera BBSRC CASE studentship project developed a Multi-Locus Sequence Typing (MLST) scheme for Paenibacillus larvae, the causative agent of American Foulbrood. Outbreaks have, since 2014, been routinely typed, and we seek to build on this work to determine the extent to which this information can be used to predict occurrence and spread of AFB.Left untreated, AFB will kill a colony of bees. Spores are fed to larvae, where they germinate in the gut, and, after the hive cell is "capped", the bacteria proliferate, eventually killing the larva and forming millions of resistant spores that are later dispersed. There are many genotypes present in the UK, and they show high levels of strain variation, defined both by the MLST and comparative genomics. Recent research shows that community diversity and competition processes in the gut microbiome encountered by pathogens is important in determining the progress and outcome of infections. The gut microbiome in turn, is determined by external environmental factors, such as food resources. We therefore hypothesise that the outcome of AFB infection in a hive is a complex interaction between disease strain genotype and the larval gut environment it encounters.The overarching aim of this project is to link genotypes within and among Clonal Complexes (CC) that have been defined by the MLST, with disease symptoms and the environment in which they occur, and to translate this into an inspection and monitoring scheme that will further contribute to keeping this destructive disease under control.The studentship will address four research areas:1) Population Genetics: Building on previous analysis (Morrissey et al. 2015; see below), and using data collected subsequently using the MLST, what is the spatial and temporal pattern of AFB outbreaks? Can Clonal complexes (CCs) be used reliably to discriminate new outbreaks from re-infections?2) Comparative Genomics: isolates collected from CCs with known distribution and disease severity, genome sequence will be determined and extensive analysis of genes related to virulence analysed.3) Environmental Genomics: what environmental factors influence the patterns of disease prevalence and severity? The student will investigate bee host gut microbiomes, and their relationship to infection by particular types of AFB.4) Practical applications: There are a number of ways in which the studies may influence screening and management of AFB. If MLST type predicts disease severity, then outbreaks can be prioritized for destruction, and follow up inspection regimes recommended. More complex environmental factors such as food resources and gut microbiomes may predict which strains successfully infect the hive, or the severity of the disease once infection becomes established. The most promising route to practical mitigation of disease will be identified and developed by the student.The project will combine genomics techniques and analysis at the University of York, with the opportunity to carry out experiments at Fera, in collaboration with the Bee Unit, and their state of the art facilities for culturing and manipulating AFB.