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: 8449371
• 负责人: Dana M Hawley
• 金额: $ 61.71万
• 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/8449371
• 关键词: Address; Back; Bacteria; Bacterial Genes; Birds; DNA; Data; Evolution; Finches; Genes; Housing; Human; Immune; Immune system; Immunity; In Vitro; Infection Control; Knowledge; Light; Measures; Modeling; Mycoplasma gallisepticum; Pattern; Public Health; Risk; Role; System; Testing; Urbanization; Vaccination; Validation; Variant; Virulence; Work; acquired immunity; anthropogenesis; feeding; gene function; in vivo; 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 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.

病原体对其宿主造成的伤害程度存在巨大差异，这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。我们建议研究一种易于处理且经过充分研究的野生动物病原体系统，即家雀及其 细菌病原体，鸡毒支原体，我们已经在其中记录了独立的 自从病原体在宿主的两个不同部分出现以来毒力不断增强的进化 范围。我们假设观察到的毒力增加模式存在两种生态条件 迄今为止检测到的进化：1）不完善的获得性宿主免疫，类似于疫苗接种，选择了更高的 宿主内病原体复制率和相关的较高毒力； 2）更高的接触率，例如 由于人类对鸟类的喂养造成的，通过最大限度地减少毒力而导致毒力增加 病原体在成功传播之前杀死宿主的风险。拟议的工作涉及整合 理论毒力模型与所提出的实验。首先，正式的主机内和主机间模型 描述这两个假设将确定模型细化和验证所需的信息；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是否 模型的假设条件解释了观察到的场模式。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异常容易处理，以便 表征部分免疫宿主与免疫初始宿主的宿主内和宿主间动态 以及主机之间的高和低接触率。补充这些以模型为中心的实验将是 来自细菌的多个现场和实验分离株的 DNA 序列和表达数据，其中我们 对鸡毒支原体基因功能的了解将使我们能够确定哪些基因可能是 检测到毒力变化。这些数据将作为部分免疫假设的独立检验 通过解决负责逃避宿主免疫系统的细菌基因是否被系统地 由于获得性免疫而在体内和体外发生选择，这与我们的假设一致。