Exploring the richness of Mycobacterium bovis strain diversity to decipher the epidemiology of bovine tuberculosis ecology

探索牛分枝杆菌菌株多样性的丰富性，解读牛结核病生态学的流行病学

• 批准号: BB/N00468X/1
• 负责人: James Wood
• 金额: $ 67.55万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN00468X%2F1
• 关键词: Exploring; richness; Mycobacterium; bovis; strain

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is a multi-species infection that causes a serious burden on the cattle industry in Great Britain (GB), and throughout the world. Despite extensive control measures in cattle, the disease in cattle remains uncontrolled and now costs the UK government around £100 million per year. Control of the disease is governed by a National Strategy, published by Defra.Control is based around routine surveillance testing of living cattle and all those slaughtered in GB slaughterhouses. Routine surveillance is based around the use of a highly specific but relatively insensitive skin test. When infection is diagnosed, attempts are made to isolate M. bovis from skin test positive cattle, which are all slaughtered. M. bovis can be isolated from around 70% of all infected herds. Herds where infection is diagnosed are placed under movement restriction and all animals are then subjected to repeated skin testing until no further detectable infection is evident. One of the great challenges for control is that half of all farms in high incidence areas of England and Wales that are restricted, tested and released have recurrent disease within 3 years. It is unclear how much of this disease burden is associated with persistence in cattle or with reintroduction from wildlife, specifically badgers, whose infection is closely linked with that in cattle in high incidence areas of GB. Thus, a key question in bTB control in Britain relates to what the source of the infection is for herd. At the individual level, knowing this allows for specific measures to be put in place to prevent recurrence of infection. At the national level, understanding the sources of constant bTB challenge, allows for more general policy to be developed and targeted at the sources of this reinfection. Modern genetic methods provide great opportunities for forensic evaluation of outbreaks of diseases. Organisms causing disease can be genetically sequenced to determine their origins and relationships with other outbreaks and cases. Detailed genetic sequencing of bacteria that cause disease is now becoming common in human medicine to determine what optimal controls should be. New methods mean that this can be done in real time. The bacterium that causes bTB, M. bovis, has been evaluated routinely in in GB using traditional genetic methods over the last 20 years as part of surveillance. These studies have the surprisingly restricted distributions of different genetic types to be mapped in Britain - and hence to determine the likely origins of outbreaks that occur in low incidence areas (often associated with cattle movements); however, the classification is not fine grained enough to allow differentiation of local on-farm persistence of disease from that associated with introduction from relatively short distance cattle movements. Our work will use the amazing library of M. bovis isolates held by Defra's laboratory agency and will apply modern whole genome sequencing methods to 2000 carefully selected retrospective samples. We will use samples from recent routine surveillance from over GB, particularly focussing on farms where disease has been persistent, to evaluate the different drivers of persistence that so hamper our control efforts. We will also use samples from the randomised badger control trial where there is unparalleled availability of badger isolates and far more intensively parallel sampled cattle to reveal more details of the complex transmission dynamic between the two species, in order to allow more precise targeting of measures to prevent cattle becoming infected in the future. Our work will translate directly into Defra's plans for more intensive investigation and intervention on farms that repeatedly become infected in high incidence areas. The approaches that we develop will become, as in human medicine, part of the routine approaches taken when investigating disease.

由牛分枝杆菌引起的牛结核病（BTB）是一种多物种感染，会严重烧毁英国（GB）以及全世界的牛业。尽管牛采取了广泛的控制措施，但牛的这种疾病仍无法控制，现在英国政府每年花费约1亿英镑。对该疾病的控制受国家战略的约束，该战略由Defra.Control出版，基于对活牛的常规监视测试以及所有在GB屠宰场被屠杀的人。常规监视是基于使用高度特异但相对不敏感的皮肤测试的。当诊断出感染时，试图将牛乳杆菌与皮肤测试阳性牛分离，这些牛都被宰杀。 Bovis M.可以与大约70％的所有受感染牛群隔离。诊断出感染的群体受到运动限制，然后对所有动物进行重复的皮肤测试，直到没有进一步可检测的感染。控制的巨大挑战之一是，在英格兰和威尔士高端事故地区的所有农场中，有一半受限制，测试和释放的农场在3年内复发。目前尚不清楚这种疾病的燃烧与牛的持久性或重新引入野生动植物，特别是badge剂，其感染与GB高入射地区的牛密切相关。这是英国BTB控制中的一个关键问题，涉及感染的根源。在个人层面上，知道这允许采取特定的措施，以防止感染复发。在国家一级，了解持续的BTB挑战的来源，可以制定和针对这种恢复的来源。现代遗传方法为疾病暴发的法医评估提供了巨大的机会。可以在遗传上测序引起疾病的生物，以确定其起源以及与其他暴发和病例的关系。细菌的详细遗传测序现在正在人类医学中变得普遍，以确定应该是什么最佳控制。新方法意味着可以实时完成。在过去的20年中，在GB中常规评估了导致BTB的细菌在GB中进行了常规评估，这是监视的一部分。这些研究具有在英国绘制的不同遗传类型的限制性分布，因此可以确定在低发射率区域（通常与牛运动有关）发生的暴发的可能起源；但是，该分类不够细的粒度，无法将局部疾病的农场持续存在与与较短的牛运动有关的疾病的引入而区分。我们的工作将使用Defra的实验室机构持有的令人惊叹的牛乳菌分离株库，并将将现代的整个基因组测序方法应用于2000年精心选择的回顾性样本。我们将使用来自GB的最新常规监视中的样本，特别是专注于持续存在的疾病的农场，以评估持久性的不同驱动因素，从而阻碍了我们的控制工作。我们还将使用来自随机badge控制试验的样品，在该试验中，无与伦比的badge分离株的可用性和更强烈的平行采样牛，以揭示两种物种之间复杂传播动态的更多细节，以便更精确地靶向措施以防止牛在未来受到感染。我们的工作将直接转化为Defra对在高发球区反复感染的农场进行更密集的投资和干预的计划。就像人类医学一样，我们开发的方法将成为研究疾病时采取的常规方法的一部分。

项目成果

Whole Genome Sequencing for Determining the Source of Mycobacterium bovis Infections in Livestock Herds and Wildlife in New Zealand.

• DOI: 10.3389/fvets.2018.00272
• 发表时间: 2018
• 期刊: Frontiers in veterinary science
• 影响因子: 3.2
• 作者: Price-Carter M;Brauning R;de Lisle GW;Livingstone P;Neill M;Sinclair J;Paterson B;Atkinson G;Knowles G;Crews K;Crispell J;Kao R;Robbe-Austerman S;Stuber T;Parkhill J;Wood J;Harris S;Collins DM
• 通讯作者: Collins DM

Population structure and transmission of Mycobacterium bovis in Ethiopia

埃塞俄比亚牛分枝杆菌的种群结构和传播

• DOI: 10.1101/2020.11.17.386748
• 发表时间: 2020
• 作者: Almaw G

Predicted structural mimicry of spike receptor-binding motifs from highly pathogenic human coronaviruses.

• DOI: 10.1016/j.csbj.2021.06.041
• 发表时间: 2021
• 期刊: Computational and structural biotechnology journal
• 影响因子: 6
• 作者: Beaudoin CA;Jamasb AR;Alsulami AF;Copoiu L;van Tonder AJ;Hala S;Bannerman BP;Thomas SE;Vedithi SC;Torres PHM;Blundell TL
• 通讯作者: Blundell TL