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

22-ICRAD 电话 2 - Q-Net-Assess（改进欧洲伯氏立克次体宿主适应和毒力的分子监测和评估）

• 批准号: BB/X020142/1
• 负责人: Tom McNeilly
• 金额: $ 58.48万
• 依托单位: Moredun Research Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX020142%2F1
• 关键词: 22; ICRAD; Call; Net; Assess

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.

Q热是由贝氏柯克斯体引起的一种重要的人畜共患病原体。人类的临床症状范围从更常见的流感样症状到持续性和潜在的致命感染。反刍家畜，特别是绵羊和山羊，是人类感染的主要来源，尽管C。贝氏体可感染多种其他动物，包括野生动物和蜱。在反刍动物中，C.贝氏体可导致流产、死胎和虚弱的后代，特别是在绵羊和山羊中，尽管大多数感染没有症状。因此，宿主范围和感染结果是高度可变的。然而，我们对C.目前主要采用的基因分型方法对C. Burnetii仅产生有限的基因组信息，且难以在实验室之间进行比对。全基因组测序（WGS）已经彻底改变了许多人畜共患病病原体的分子流行病学和监测，因为它提供了全面的遗传信息，并且易于标准化。然而，C.由于从野外样品中分离细菌的困难，我们已经组建了一个具有独特的C. burnetii监测和基因组学，使整理C。来自广泛宿主（牲畜、野生动物和人类）的贝氏阳性样本，具有准确的临床数据。C.将使用优化的分离方法从这些样品中分离伯内特氏菌。分离的菌株，加上可用的存档菌株，将提交给WGS，以生成一个全面的注释C。贝氏体基因组，其中将包括来自田间和体外细胞测定的表型数据。WGS数据将使用新的生物信息学方法进行分析，以确定C的分子决定簇。贝氏虫的寄主范围和毒力。最后，项目成果将被综合成一个推荐的框架，用于未来的C。伯内特氏菌