The molecular basis and impact on host response of phenotypic variation across Mycobacterium bovis molecular types

牛结核病（bTB）是当今英国农业面临的最困难的动物健康问题之一。感染bTB的牛的数量逐年增加18%，由于屠宰受感染的动物和实施牛的流动限制，这给受影响的农场造成了严重损失。政府在疾病监测和农民补偿方面的支出也呈上升趋势，2004-2012年期间的支出预计将超过10亿英镑。从这些统计数字可以清楚地看出，目前的疾病控制战略没有发挥作用，但其原因并不明显。一种可能性是，结核分枝杆菌（Mycobacterium bovis）这种新形式的病原体已经在英国进化，能够绕过目前的控制措施。VLA的研究发现，后一种情况的证据得到了在英国流行的一系列不同类型的牛支原体的支持，这些牛支原体似乎成功地从最初的隔离地传播到全国各地。这一提议旨在确定这些不同类型的牛分枝杆菌是否以不同的方式与牛的免疫系统相互作用，从而解释它们的成功。为了实现这一目标，我们将利用最近获得的牛分枝杆菌和牛宿主的完整DNA序列。这将使我们能够探索宿主和病原体如何在单个分子水平上相互作用，并建立一个更详细的牛分枝杆菌如何在牛中引起疾病的图像。来自该项目的信息将帮助政府决策者在利用流行病学信息的基础上制定新的控制战略，并提供机会阻止英国结核分枝杆菌疾病负担和相关支出的螺旋式上升。

Bovine tuberculosis (bTB) is one of the most difficult animal health problems that the farming industry in Great Britain faces today. The number of cattle infected with bTB has been increasing year on year by 18%, which leads to serious losses for affected farms due to the slaughter of infected animals and the imposition of cattle movement restrictions. Government spending on disease surveillance and compensation to farmers has also been following this upward trend, with spending over 2004-2012 expected to top £1 billion. From these statistics it is clear that the current disease control strategy is not working, yet the reasons for this are not obvious. One possibility is that new forms of the causative agent of bTB, Mycobacterium bovis, have evolved in GB that are able to circumvent the current control measures. Research by the VLA has found that evidence for this latter scenario is supported by the presence of a range of different types of M. bovis circulating in GB that seem to be successful in spreading around the country from their original place of isolation. This proposal sets out to determine whether these diverse types of M. bovis interact with the immune system of cattle in different ways, and so explain their success. To achieve this we will take advantage of the recent availability of the complete DNA sequences of both M. bovis and the bovine host. This will allow us to explore how the host and pathogen interact with each other at the level of individual molecules, and to build up a more detailed picture of how M. bovis causes disease in cattle. The information coming from this project will help government policy makers to develop new control strategies based on the exploitation of epidemiological information, and offers the chance to stop the upward spiral of bTB disease burden and linked expenditure in GB.