Ecological drivers of virulence evolution in an emerging avian pathogen

病原体对宿主造成的危害程度的广泛变化引起了生物学家的兴趣， 几个世纪以来，但令人惊讶的是，在非实验室中测试理论预测的机会很少。 系统.我们提出了一个易于处理的和充分研究的野生动物病原体系统，家雀及其 细菌病原体，鸡毒支原体，其中我们已经记录了独立的 自病原体在宿主的两个不同部分出现以来， 范围我们假设两种生态条件是观察到的毒性增加模式的基础 迄今为止发现的进化：1）不完全的获得性宿主免疫，类似于疫苗接种，选择了较高的 宿主内病原体复制率和相关的较高毒力; 2）较高的接触率，如 由于人类喂饲鸟类而引起的， 病原体在成功传播之前杀死宿主的风险。拟议的工作包括： 理论毒力模型与拟议的实验。第一，正式的主机内和主机间模型 描述这两个假设将识别模型改进和验证所需的信息;第二， 有针对性的实验将量化关键参数;第三，这些数据将反馈，以评估 这些模型的假设条件解释了观测到的磁场模式。经验数据将来自受控的 感染和传播实验，在我们的研究系统中异常容易处理， 表征部分免疫与免疫初始宿主的宿主内和宿主间动力学 以及宿主间的高接触率和低接触率。补充这些以模型为中心的实验将是 DNA序列和表达数据，从多个领域和实验分离的细菌，其中我们的 对M.鸡毒败血症将使我们能够确定哪些基因可能导致 检测到毒力变化。这些数据将作为部分免疫假说的独立检验 通过研究细菌基因是否系统地逃避宿主免疫系统， 由于获得性免疫，在体内和体外的选择下发生变化，与我们的假设一致。

The extensive variation in the amount of harm that pathogens cause their hosts has intrigued biologists for centuries, but there have been surprisingly few opportunities to test theoretical predictions in non-laboratory systems. We propose work on a tractable and well-studied wildlife-pathogen system, the house finch and its bacterial pathogen, Mycoplasma gallisepticum, in which we have already documented the independent evolution of increasing virulence since the emergence of the pathogen in two distinct parts of the host's range. We hypothesize two ecological conditions that underiie the observed patterns of increasing virulence evolution detected to date: 1) imperfect acquired host immunity, akin to vaccination, has selected for higher rates of within-host pathogen replication and associated higher virulence; and 2) higher contact rates, such as caused by anthropogenic feeding of birds, have resulted in increased virulence by minimizing the pathogen's risk of killing its host before it successfully transmits. The proposed work involves integration of theoretical virulence models with proposed experiments. First, formal within- and between-host models describing the two hypotheses will identify information needed for model refinement and validation; second, targeted experiments will quantify key parameters; and, third, these data will feed back to evaluate whether the models' assumed conditions explain observed field patterns. The empirical data will come from controlled infection and transmission experiments, which are unusually tractable in our study system, in order to characterize within- and between-host dynamics for partially immune versus immunologically naive hosts and at high and low between-host contact rates. Supplementing these model-focused experiments will be DNA.sequence and expression data from multiple field and experimental isolates of the bacteria, where our knowledge of gene function in M. gallisepticum will allow us to identify which genes may underiie the detected virulence changes. These data will serve as an independent test of the partial immunity hypothesis by addressing whether bacterial genes responsible for evading host immune systems are systematically changing in vivo and in vitro under selection due to acquired immunity, consistent with our hypothesis.