Host and vector adaptation in the tick-borne human pathogens Borrelia

为了能够生存，寄生媒介传播的细菌已经开发了一系列复杂的手段来适应它们的宿主和媒介。它们的分布受到储集宿主和感受态载体的限制。生态条件，如宿主的可用性，以及遗传漂变等随机过程，都可能导致细菌从一种宿主类型转换到另一种宿主类型或适应新的载体。了解哪些基因参与这种适应可以帮助控制这些病原体并确定新的疾病预防策略。在这里，我们计划使用人口基因组学方法，以确定在两个细菌物种负责莱姆病宿主和载体适应的遗传因素：Borrelia garinii和B。巴伐利亚人这两个物种都存在于欧洲和亚洲，都是人类病原体。它们的区别在于用作宿主的动物类型和B。bavariensis由至少两个使用不同蜱媒介物种的分离种群组成。在我们的研究中，我们将使用来自东亚，西欧和俄罗斯的菌株重建这两个物种的进化历史。然后，我们将研究在宿主和/或载体适应中发挥作用的候选基因的进化（编码所谓的CRASP蛋白，即补体调节因子获得表面蛋白），并测试这些基因是否处于选择压力下。接下来，我们将确定新的基因选择，可能是负责宿主或载体适应在两个物种的研究。最后，我们将寻找这些基因在宿主或载体中感染和存活中所起作用的功能验证。我们的研究将允许解开宿主和载体适应的遗传基础，在两个物种的研究，也了解宿主和载体开关可以发生在疏螺旋体。这是流行病学的重要性，因为它将有助于预测不同疏螺旋体物种的传播，这取决于可能因气候变化而变化的宿主和媒介的种群。我们的研究也将最终有助于理解为什么某些疏螺旋体物种是人类致病性的，以及参与人类免疫系统逃避的遗传机制是如何进化的。

To be able to survive, parasitic vector-borne bacteria have developed a range of sophisticated means to adapt to their hosts and vectors. Their distribution is constrained by that of reservoir hosts and competent vectors. Ecological conditions, such as the availability of hosts, but also random processes such as genetic drift, can lead the bacteria to switch from one host type to another or to adapt to a new vector. Knowing which genes are involved in this adaptation can help to control those pathogens and identify novel disease prevention strategies. Here we plan to use population genomics methods to identify genetic factors involved in host and vector adaptation in two bacteria species responsible for Lyme disease: Borrelia garinii and B. bavariensis. Both species are present in Europe and Asia and both are human pathogens. They differ by the type of animal used as reservoir-host and B. bavariensis is composed of at least two separated populations using different tick vector species. In our study we will reconstruct the evolutionary history of these two species using strains from Eastern Asia, Western Europe and Russia. We will then study the evolution of genes that are candidates for playing a role in host and/or vector adaptation (encoding the so-called CRASP proteins for Complement Regulator-Acquiring Surface Proteins) and test whether these genes are under selective pressure. Next, we will identify novel genes under selection that might be responsible for host or vector adaptation in the two species under study. Finally, we will look for functional validation of the role played by those genes in infection and survival in the host or the vector. Our study will allow to unravel the genetic basis of host and vector adaptation in the two species under study and also to understand how host and vector switches can occur in Borrelia. This is of epidemiological importance as it will help to predict the spread of the different Borrelia species depending on the populations of hosts and vectors that might vary due to climate change. Our study will also ultimately contribute to the understanding of why certain Borrelia species are human pathogenic and how the genetic mechanisms involved in human immune system evasion evolved.