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Palaeopopulation genomics of Mycobacterium tuberculosis

结核分枝杆菌古种群基因组学

基本信息

批准号：
NE/K012185/1
负责人：
Terence Brown
金额：
$ 49.58万
依托单位：
University of Manchester
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=NE%2FK012185%2F1
关键词：
Palaeopopulation genomics Mycobacterium tuberculosis

项目摘要

Tuberculosis is a reemerging infection that was also common in the past in Britain. Poverty, drug resistance, AIDS and migration are key factors in its occurrence today. The disease is usually caused by the bacterium called Mycobacterium tuberculosis, which exists as a variety of strains that have different degrees of virulence and are found in different parts of the world. Most tuberculosis infections occur in the lungs, because it is transmitted via coughing, but other parts of the body can also be infected, especially if the disease is caught by eating or drinking infected foods. If left untreated the infection can cause damage to different bones in the body, most commonly the spine, ribs, hips and knees. Archaeologists have used this information to study tuberculosis in the past, but visual examination of skeletons does not reveal which of the various strains of M. tuberculosis is present. We would like to be able to distinguish different strains of M. tuberculosis in archaeological remains because this would enable us to study the evolution of the disease. We could, for example, ask if different strains of tuberculosis were present in different parts of Britain, and in particular if people living in the countryside and in towns were exposed to different types of tuberculosis. We could also examine how tuberculosis evolved in response to the increased urbanization that occurred during the Mediaeval period. Until recently it was impossible to identify the particular strain of M. tuberculosis present in a skeleton, but now there are techniques for studying the small amounts of 'ancient' DNA that are preserved in some samples. In a previous project we used these methods with 491 skeletons from 145 archaeological sites from across all of Britain and Europe, most of these skeletons showing signs of tuberculosis, and dating from the Roman period to the 19th century AD. About half of the skeletons did not appear to contain any ancient DNA, but we achieved positive detections with enough samples to believe that meaningful comparisons can be made between tuberculosis strains from different places and periods. In the proposed project we will use new methods for sequencing ancient DNA in order to obtain the detailed information we need in order to compare an archaeological variety of M. tuberculosis with modern strains of the bacterium. We have already shown that these methods work, because we have used them successfully with one skeleton, of an adolescent female from 19th century Leeds, England. We showed that this person had been infected with a strain of tuberculosis that is rare today, but which we think was much more common in the past. In the new project we intend using the same approach with 24 skeletons, 22 from Britain, one from France and one from the Ukraine. We hope to be able to obtain equally detailed information on the strains of tuberculosis in these other skeletons, and hence to show that ancient DNA sequencing has genuine potential as a means of studying the evolution of tuberculosis.

结核病是一种重新出现的感染，过去在英国也很常见。贫穷、抗药性、艾滋病和移民是今天发生这种情况的关键因素。这种疾病通常是由一种名为结核分枝杆菌的细菌引起的，这种细菌以各种毒力不同的菌株存在，在世界不同地区都有发现。大多数肺结核感染发生在肺部，因为它通过咳嗽传播，但身体其他部位也可能被感染，特别是如果疾病是通过食用或饮用受感染的食物感染的。如果不治疗，感染会对身体的不同骨骼造成损害，最常见的是脊柱、肋骨、臀部和膝盖。考古学家过去曾使用这些信息来研究结核病，但对骨骼的肉眼检查并不能揭示存在哪种不同的结核分枝杆菌菌株。我们希望能够在考古遗迹中区分不同的结核分枝杆菌菌株，因为这将使我们能够研究这种疾病的进化。例如，我们可以问，英国不同地区是否存在不同类型的结核病，特别是居住在农村和城镇的人是否接触到不同类型的结核病。我们还可以研究结核病是如何随着中世纪时期城市化程度的提高而演变的。直到最近，还不可能识别骨骼中存在的特定结核分枝杆菌菌株，但现在有了技术来研究保存在一些样本中的少量“古老”DNA。在之前的一个项目中，我们使用了这些方法，对来自英国和欧洲各地145个考古遗址的491具骨骼进行了研究，其中大多数骨骼显示出肺结核的迹象，可以追溯到罗马时期到公元19世纪。大约一半的骨骼似乎不包含任何古代DNA，但我们通过足够的样本获得了积极的检测，相信可以在不同地点和时期的结核病菌株之间进行有意义的比较。在拟议的项目中，我们将使用新的方法对古代DNA进行测序，以获得我们需要的详细信息，以便将一种考古的结核分枝杆菌与现代菌株进行比较。我们已经证明了这些方法是有效的，因为我们已经成功地将它们用于19世纪英国利兹的一具青少年女性的骨架上。我们发现这个人感染了一种结核病菌株，这种菌株在今天很罕见，但我们认为在过去更常见。在新的项目中，我们打算使用同样的方法来处理24具骨架，其中22具来自英国，一具来自法国，一具来自乌克兰。我们希望能够获得这些其他骨骼中结核菌株的同样详细的信息，从而表明古代DNA测序作为研究结核病进化的一种手段具有真正的潜力。