Dissecting the molecular diversity of bovine digital dermatitis treponemes.

剖析牛指皮炎密螺旋体的分子多样性。

• 批准号: BB/K009443/1
• 负责人: Nicholas Evans
• 金额: $ 44.86万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FK009443%2F1
• 关键词: Dissecting; molecular; diversity; bovine; digital

Bovine Digital Dermatitis (BDD) is a lameness of cattle present in the majority of dairy herds in the UK and reported throughout the world. This lameness is the result of inflamed lesions between the heel bulbs of the rear feet. The disease is of particular significance because it is very painful for the animal affected resulting in poor animal welfare. Despite some response to commonly used antibiotics, lesions frequently reappear. The disease is an important global food security issue because it causes reduction in milk production and poor reproductive performance in dairy cows. Furthermore, with the recent cost to the dairy industry in the UK likely to be as much as 26 million pounds per year, it has a negative effect the UK's economic competitiveness. The disease has now been identified in sheep, where it is known as Contagious Ovine Digital Dermatitis (CODD) with lesions more severe than seen in cattle with frequent reports of complete hoof loss. BDD has been identified as an infectious disease with a bacterial cause. The majority of evidence clearly identifies bacteria known as 'Treponema' as the common cause of BDD. Previous studies at the University of Liverpool have clarified the association of these bacteria with BDD and characterised these causal bacteria into three distinct groups. These studies have allowed for the isolation of 70 treponemes from BDD lesions, a greater number than any other research groups working on this disease worldwide. This strain collection is an invaluable resource for investigating how these organisms produce such severe disease in cattle and sheep and how the infection may so readily be transmitted between animals. The proposed research in this current grant application will use this large panel of isolates to investigate how these organisms cause the disease in cattle and whether novel vaccines or treatments can be developed. The three distinct groups of bacteria (treponemes) are very different from one another in terms of their genetics and their actual characteristics yet they are all able to colonise the bovine hoof and cause disease. Whilst the different treponeme groups may be quite diverse, to be able to share the same 'niche', they may still share very similar machinery to be able to grow, survive and damage the cow. This common machinery is likely to be proteins exhibited on the surface of the cell which are responsible for binding or damaging the host and if shared across all BDD treponemes may have potential as vaccine targets. Identification of these key bacterial proteins and determining whether they interact with the host immune system allows for identification of potential vaccine components and thus enable a strategy to prevent disease in cattle and sheep herds.At the University of Liverpool, there have been major investments in the current cutting edge technologies of genomics and proteomics and with these facilities it is now possible to perform substantial experiments not previously possible. For example, whole genomes of these treponemes can now be generated in a relatively short time. This study proposes to use this cutting edge sequencing technology to investigate, on a large scale all the predicted disease causing characteristics of the bacteria. To confirm that the genes identified are in fact expressed the proteomics approaches will be used to identify all the proteins both inside the treponemes and those on the surface. Furthermore cattle sera will be incubated with the bacterial cell surface proteins to identify which cell surface proteins are bound to by antibodies and therefore to actually identify which are detected by the cattle's immune system. These studies will help characterise the causal bacteria and further aid in potential vaccine design. By investigating BDD using the various methods described above, we should improve understanding of the disease and contribute towards the eradication of this painful and expensive disease.

牛数字化跛行（BDD）是一种存在于英国大多数奶牛群中的牛跛行，并在世界各地报道。这种跛行是由于后足的足跟球之间的发炎病变。该疾病具有特别重要的意义，因为它对受影响的动物非常痛苦，导致动物福利差。尽管对常用的抗生素有一些反应，但病变经常复发。该疾病是一个重要的全球粮食安全问题，因为它会导致牛奶产量减少和奶牛繁殖性能下降。此外，最近英国乳制品行业的成本可能高达每年2600万英镑，这对英国的经济竞争力产生了负面影响。这种疾病现在已经在绵羊中被发现，它被称为传染性绵羊趾皮病（CODD），其病变比在牛中看到的更严重，经常报告完全丧失蹄。BDD已被确定为一种由细菌引起的传染病。大多数证据清楚地表明，被称为“密螺旋体”的细菌是BDD的常见原因。利物浦大学先前的研究已经阐明了这些细菌与BDD的关联，并将这些致病细菌分为三个不同的组。这些研究已经从BDD病变中分离出70种密螺旋体，比世界上任何其他研究这种疾病的研究小组都要多。这种菌株的收集是研究这些生物如何在牛和羊中产生如此严重的疾病以及感染如何在动物之间传播的宝贵资源。目前拨款申请中的拟议研究将使用这一大型分离物小组来研究这些生物体如何在牛中引起疾病，以及是否可以开发新的疫苗或治疗方法。这三种不同的细菌（密螺旋体）在遗传学和实际特征方面彼此非常不同，但它们都能够在牛蹄上定居并引起疾病。虽然不同的密螺旋体组可能非常不同，能够共享相同的“生态位”，但它们仍然可能共享非常相似的机制，能够生长，存活和损害奶牛。这种常见的机制可能是细胞表面上表现出的蛋白质，其负责结合或损伤宿主，并且如果在所有BDD密螺旋体中共享，则可能具有作为疫苗靶标的潜力。鉴定这些关键的细菌蛋白并确定它们是否与宿主免疫系统相互作用，可以鉴定潜在的疫苗成分，从而实现预防牛和羊群疾病的策略。在利物浦大学，在目前的基因组学和蛋白质组学尖端技术方面已经有了重大投资，有了这些设施，现在可以进行以前没有的大量实验。可能例如，现在可以在相对较短的时间内生成这些密螺旋体的整个基因组。这项研究建议使用这种尖端的测序技术来大规模调查细菌的所有预测致病特征。为了证实所鉴定的基因实际上是表达的，蛋白质组学方法将用于鉴定密螺旋体内部和表面上的所有蛋白质。此外，牛血清将与细菌细胞表面蛋白一起孵育，以鉴定抗体与哪些细胞表面蛋白结合，从而实际鉴定哪些被牛的免疫系统检测到。这些研究将有助于鉴定致病细菌，并进一步帮助潜在的疫苗设计。通过使用上述各种方法调查BDD，我们应该提高对这种疾病的理解，并为根除这种痛苦而昂贵的疾病做出贡献。

项目成果

Multilocus Sequence Typing of Pathogenic Treponemes Isolated from Cloven-Hoofed Animals and Comparison to Treponemes Isolated from Humans.

• DOI: 10.1128/aem.00025-16
• 发表时间: 2016-08-01
• 期刊: Applied and environmental microbiology
• 影响因子: 4.4
• 作者: Clegg SR;Carter SD;Birtles RJ;Brown JM;Hart CA;Evans NJ
• 通讯作者: Evans NJ

Survival of contagious ovine digital dermatitis (CODD)-associated treponemes on disposable gloves after handling CODD-affected feet.

• DOI: 10.1136/vr.104228
• 发表时间: 2017-07-22
• 期刊: The Veterinary record
• 作者: Angell JW;Clegg SR;Grove-White DH;Blowey RW;Carter SD;Duncan JS;Evans NJ
• 通讯作者: Evans NJ

In vitro susceptibility of contagious ovine digital dermatitis associated Treponema spp. isolates to antimicrobial agents in the UK.

• DOI: 10.1111/vde.12269
• 发表时间: 2015-12
• 期刊: Veterinary dermatology
• 影响因子: 1.4
• 作者: Angell JW;Clegg SR;Sullivan LE;Duncan JS;Grove-White DH;Carter SD;Evans NJ
• 通讯作者: Evans NJ

Digital dermatitis treponemes: different pathology, different host species, but same bacteria?

指趾皮炎密螺旋体：不同的病理，不同的宿主物种，但相同的细菌？

• 发表时间: 2016
• 作者: Clegg S.R.