Ecological drivers of virulence evolution in an emerging avian pathogen

新兴禽类病原体毒力进化的生态驱动因素

• 批准号: 8545883
• 负责人: Dana M Hawley
• 金额: $ 53.02万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8545883
• 关键词: Address; Archives; Back; Bacteria; Bacterial Genes; Biological; Birds; Boxing; Communities; DNA; Data; Development; Environment; Evolution; Finches; Genes; Housing; Human; Immune; Immune system; Immunity; In Vitro; Infection Control; Knowledge; Light; Maps; Measures; Medical; Modeling; Molecular; Mycoplasma gallisepticum; Pattern; Play; Process; Public Health; Research; Risk; Role; Songbirds; System; Testing; Urbanization; Vaccination; Validation; Variant; Virulence; Work; acquired immunity; anthropogenesis; base; feeding; gene function; in vivo; insight; killings; pathogen; research study; transmission process

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.

几个世纪以来，病原体对宿主造成的危害程度的广泛变化一直吸引着生物学家，但令人惊讶的是，在非实验室系统中测试理论预测的机会很少。我们提出了一个易于处理的和良好的研究野生动物的病原体系统，家雀和它的细菌病原体，鸡毒支原体，在其中我们已经记录了独立的进化，因为出现的病原体在两个不同的部分主机的范围内的毒力增加。我们假设两种生态条件是迄今为止检测到的毒力进化增加的观察模式的基础：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 由于人为喂养鸟类而引起的感染，通过最大限度地减少病原体在成功传播之前杀死其宿主的风险，导致了毒力的增加。拟议的工作涉及整合的理论毒力模型与拟议的实验。首先，描述这两个假设的正式宿主内和宿主间模型将确定模型改进和验证所需的信息;其次， 有针对性的实验将量化关键参数;第三，这些数据将反馈，以评估模型的假设条件是否解释了观察到的场模式。经验数据将来自控制感染和传播实验，这是非常容易处理的，在我们的研究系统中，为了表征内和宿主之间的动态部分免疫与免疫幼稚的主机，并在高和低主机之间的接触率。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，其中我们的知识，基因功能的M。鸡毒败血症将允许我们鉴定哪些基因可能是检测到的毒力变化的基础。这些数据将作为一个独立的测试部分免疫假说，解决是否细菌基因负责逃避宿主免疫系统的系统性变化，在体内和体外的选择下，由于获得性免疫，与我们的假设一致。