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.

病原体引起的宿主的危害量的广泛差异已经吸引了生物学家几个世纪，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。我们提出了关于可探索且研究充分的野生动物病原体系统的工作，房屋雀科及其细菌病原体，分枝杆菌小肠菌，我们已经记录了自从宿主两个不同部分中病原体出现以来，我们已经记录了增加毒力的独立演变。我们假设两种生态条件是观察到的毒力进化增加的模式的基础：1）迄今为止不完善的获得的宿主免疫，类似于疫苗接种，已选择以较高的宿主内病原体复制率和相关的较高的毒力； 2）更高的接触率，这样 由于鸟类的人为喂养引起的，通过最大程度地减少病原体在成功传播之前杀死其宿主的风险，从而增加了毒力。提出的工作涉及将理论毒力模型与提出的实验整合在一起。首先，描述这两个假设的正式内部和主机间模型将确定模型改进和验证所需的信息；第二， 目标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现场模式。经验数据将来自受控感染和传播实验，这些实验在我们的研究系统中与众不同，以表征部分免疫与免疫学幼稚的宿主以及主机之间的宿主内部和间动力学之间的特征，并且在主持人之间的接触率高和低接触率。补充这些以模型为中心的实验将是 DNA，来自多个领域和实验分离株的序列和表达数据，在该细菌中，我们对Gallisepticum M. clisepticum中的基因功能的了解将使我们能够识别哪些基因可以低于检测到的毒力变化。这些数据将通过解决负责逃避宿主免疫系统的细菌基因是否系统地在体内和由于获得的免疫力而在选择下在体外进行系统改变，这将作为对部分免疫力假设的独立检验。