Bacterial Determinants of Tuberculosis Susceptibiliy

项目2：细菌易感性决定因素 摘要： 结核病感染的结果因人而异；大多数人没有表现出 疾病，但有些人会发展为进行性疾病。这些结果的差异似乎出现在两种情况下 因为人与人之间的差异，也因为分枝杆菌菌株之间的差异 他们感染的肺结核。事实上，人类的基因差异似乎与细菌相互作用 差异，即相同的细菌可能能够在一个宿主上致病，但不能在另一个宿主上致病 同样，一个人可能对某一种细菌敏感，但对另一种细菌不敏感。在这个项目中，我们寻求 了解这种细菌特征与宿主遗传学的交集，我们称之为“宿主-病原体” 偏好“。在目标1中，我们将通过测试来确定影响寄主-病原体偏好的细菌因素 大量结核分枝杆菌菌株在一组高度多样化的小鼠中生长( CC小鼠)。我们将确定细菌和宿主遗传标记的相互作用，这很可能导致 并将测试这些标志物预测人类疾病的能力。目标2，我们将确定 一些细菌菌株比其他细菌菌株毒力更强的机制。最后，在目标3中，我们将测试 假设卡介苗接种可以预防某些结核分支杆菌菌株的感染，但不能预防其他菌株的感染。 这些研究还将使我们能够开发结核分枝杆菌感染的实验模型，反映 人类面临的细菌多样性，并为更成功的疫苗和治疗提供了一条途径 测试。

Project 2: Bacterial Determinants of Susceptibility Abstract: The outcome of tuberculosis infection varies tremendously between individuals; most people show no signs of disease but some people will develop progressive disease. These differences in outcome seem to arise both because of differences between people but also because of differences between the strains of Mycobacterium tuberculosis with which they are infected. Indeed, human genetic differences seem to interact with bacterial differences such that the same bacterium may be able to cause disease in one host but not another and similarly, one person may be susceptible to a given bacterium but not another. In this project, we seek to understand this intersection of bacterial features with host genetics, which we term “host-pathogen preference”. In Aim 1, we will define the bacterial factors that influence host-pathogen preference by testing the growth of a very large number of M. tuberculosis strains in a panel of mice bred to be highly diverse (the CC mice). We will identify bacterial and host genetic markers for interactions that are very likely to cause disease and will test the ability of these markers to predict human disease. Aim 2, we will determine the mechanisms by which some bacterial strains are more virulent than others. Finally, in Aim 3, we will test the hypothesis that BCG vaccination protects against infection with some M. tuberculosis strains but not others. These studies will also allow us to develop experimental models of M. tuberculosis infection that reflect the diversity of bacteria that humans face and provide an avenue for more successful vaccine and therapeutic testing.