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.

牛结核病（bTB）是由牛分枝杆菌（Mycobacterium bovis）引起的多物种感染，其对英国（GB）和全世界的养牛业造成严重负担。尽管对牛采取了广泛的控制措施，但牛的疾病仍然不受控制，现在英国政府每年花费约1亿英镑。该疾病的控制由Defra发布的国家战略管理。控制基于对活牛和所有在GB屠宰场屠宰的牛的常规监测测试。常规监测是基于使用高度特异性但相对不敏感的皮肤试验。当确诊感染时，尝试分离M。从皮试呈阳性的牛身上提取的牛，这些牛都被屠宰了。M.牛可以从大约70%的受感染牛群中分离出来。对诊断出感染的畜群进行活动限制，然后对所有动物进行重复皮肤测试，直到没有进一步可检测到的感染。控制面临的最大挑战之一是，英格兰和威尔士高发病率地区的所有农场中，有一半在3年内受到限制，测试和释放。目前还不清楚这种疾病的负担有多少与牛的持久性或从野生动物，特别是獾，其感染与GB的高发地区的牛密切相关的重新引入。因此，英国bTB控制的一个关键问题涉及牛群的感染源。在个人层面上，了解这一点可以制定具体措施，以防止感染复发。在国家一级，了解持续的bTB挑战的来源，可以制定更一般的政策，并针对这种再感染的来源。现代遗传学方法为疾病暴发的法医学评估提供了巨大的机会。可以对引起疾病的生物体进行基因测序，以确定其起源以及与其他疫情和病例的关系。致病细菌的详细基因测序现在在人类医学中变得越来越普遍，以确定最佳控制应该是什么。新的方法意味着这可以在真实的时间内完成。引起bTB的细菌M.在过去的20年里，作为监测的一部分，在GB中使用传统的遗传学方法对牛进行了常规评价。这些研究令人惊讶地限制了不同遗传类型在英国的分布，从而确定了发生在低发病率地区（通常与牛群移动有关）的疫情的可能起源;然而，分类不够精细，无法区分当地农场持续存在的疾病与相对短距离的牛群移动带来的疾病。我们的工作将使用令人惊叹的M. Defra实验室机构持有的牛分离物，并将应用现代全基因组测序方法对2000个精心挑选的回顾性样本进行测序。我们将使用最近来自GB以上的常规监测样本，特别是关注疾病持续存在的农场，以评估阻碍我们控制工作的不同持续性驱动因素。我们还将使用来自随机化獾控制试验的样本，其中有无与伦比的獾分离株和更密集的平行采样牛，以揭示两个物种之间复杂的传播动态的更多细节，以便更精确地定位措施，以防止牛在未来被感染。我们的工作将直接转化为Defra的计划，对高发地区反复感染的农场进行更深入的调查和干预。我们开发的方法将成为人类医学研究疾病时常规方法的一部分。

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