22-ICRAD Call 2 - Q-Net-Assess (Improved molecular surveillance and assessment of host adaptation and virulence of Coxiella burnetii in Europe)

Q热是由伯氏柯克斯体引起的一种重要的人畜共患病病原体。人类的临床症状从更常见的流感样症状到持续的、可能致命的感染。反刍动物家畜，特别是绵羊和山羊，是人类感染的主要来源，尽管布氏梭菌可以感染包括野生动物和扁虱在内的各种其他动物。在反刍动物中，布氏梭菌可导致流产、死产和后代虚弱，特别是在绵羊和山羊身上，尽管大多数感染是无症状的。因此，感染的宿主范围和结果是高度可变的。然而，我们对伯氏梭菌基因型如何导致这种变异的了解是有限的。目前用于伯氏梭菌的主要基因分型方法只能产生有限的基因组信息，并且很难在实验室之间标准化。全基因组测序(WGS)提供了全面的遗传信息，且易于标准化，使许多人畜共患病病原体的分子流行病学和监测发生了革命性的变化。然而，目前可用于WGS的伯氏弧菌菌株很少，这主要是由于从现场样本中分离细菌的困难。我们已经组建了一个在伯氏弧菌监测和基因组学方面具有独特专业知识的财团，以允许从广泛的宿主(牲畜、野生动物和人类)中收集具有准确临床数据的伯氏弧菌阳性样本。将使用优化的分离方法从这些样本中分离出伯氏梭菌。分离的菌株，加上可用的存档菌株，将被提交给WGS，以生成一个带注释的伯氏梭菌基因组的综合数据库，其中将包括来自现场和体外细胞分析的表型数据。WGS数据将使用新的生物信息学方法进行分析，以确定伯氏梭菌寄主范围和毒力的分子决定因素。最后，项目成果将被综合成一个推荐的框架，用于未来对伯氏梭菌的分子监测。

Q fever is an important zoonotic pathogen caused by the bacterium Coxiella burnetii. Clinical signs in humans range from more common flu-like symptoms to persistent and potentially fatal infections. Ruminant livestock, and sheep and goats in particular, are the primary source of human infections, although C. burnetii can infect a wide range of other animals including wildlife and ticks. In ruminants, C. burnetii can cause abortion, stillbirth and weak offspring, particularly in sheep and goats, although most infections are asymptomatic. Thus, host range and outcome of infection is highly variable. However, our understanding of how C. burnetii genotype contributes to this variation is limited.The main genotyping methods currently used for C. burnetii generate only limited genomic information and are difficult to standardise between laboratories. Whole genome sequencing (WGS) has revolutionised molecular epidemiology and surveillance of many zoonotic pathogens as it provides comprehensive genetic information and is easily standardised. However, few C. burnetii strains are currently available for WGS, largely due to difficulties in isolating the bacteria from field samples.We have assembled a consortium with unique expertise in C. burnetii surveillance and genomics to allow collation of C. burnetii positive samples from a wide range of hosts (livestock, wildlife and humans) with accurate clinical data. C. burnetii will be isolated from these samples using optimised isolation methods. Isolated strains, plus available archived strains, will be submitted for WGS to generate a comprehensive database of annotated C. burnetii genomes, which will include phenotypic data from the field and in-vitro cellular assays. WGS data will be analysed using novel bioinformatics approaches to identify molecular determinants of C. burnetii host range and virulence. Finally, project outputs will be synthesised into a recommended framework for future molecular surveillance of C. burnetii.