Ecological drivers of virulence evolution in an emerging avian pathogen

几个世纪以来，病原体对宿主造成的危害程度的广泛差异一直吸引着生物学家的兴趣，但令人惊讶的是，在非实验室系统中检验理论预测的机会很少。我们建议对一个易于驯化和研究充分的野生动物-病原体系统--家雀及其细菌病原体--鸡毒支原体进行研究，在该系统中，我们已经证明了自从病原体在宿主范围的两个不同部分出现以来，毒力不断增加的独立进化。我们假设了两个生态条件，它们是迄今为止观察到的毒力进化模式的基础：1)不完美的获得性宿主免疫，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；以及2)较高的接触率，如 由于人类对鸟类的喂养造成的，通过将病原体在成功传播之前杀死其宿主的风险降至最低，导致了毒力的增加。拟议的工作包括将理论毒力模型与拟议的实验相结合。首先，描述这两个假设的主机内和主机之间的正式模型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，这些数据将反馈评估模型的假设条件是否解释了观测到的场模式。经验数据将来自受控感染和传播实验，在我们的研究系统中，这些实验非常容易处理，以表征部分免疫的宿主与免疫幼稚的宿主之间的动态以及在宿主间接触率高和低的情况下。补充这些以模型为重点的实验将是 来自多个现场和实验分离的细菌的DNA序列和表达数据，我们对鸡败血杆菌基因功能的了解将使我们能够确定哪些基因可能影响检测到的毒力变化。这些数据将作为部分免疫假说的独立检验，解决负责逃避宿主免疫系统的细菌基因在体内和体外是否由于获得性免疫而发生系统变化，这与我们的假设一致。

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 underlie 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.